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1
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Gao Y, Tang Y. Emerging roles of prohibitins in cancer: an update. Cancer Gene Ther 2025; 32:357-370. [PMID: 40057573 DOI: 10.1038/s41417-025-00883-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Revised: 02/17/2025] [Accepted: 02/26/2025] [Indexed: 04/09/2025]
Abstract
The prohibitin (PHB) family, including PHB1 and its homolog PHB2, is ubiquitously located in different cellular compartments and plays roles in fundamental cellular processes such as proliferation, differentiation, and apoptosis. Accumulating evidence has indicated that this family contributes to the development of numerous diseases in particular cancers. Aberrant expressions of PHBs can been observed in diverse types of human cancer. Depending on their cell compartment-specific attributes and interacting proteins, PHBs are tightly linked to almost all aspects of cancer biology and have distinct bidirectional functions of tumor-suppression or tumor-promotion. However, the roles of PHBs in cancer have yet to be fully characterized and understood. This review provides an updated overview of the pleiotropic effects of PHBs and emphasizes their characteristic roles in each cancer respectively, with the great expectation to identify potential targets for therapeutic approaches and promising molecular biomarkers for cancer diagnosis and prognostic monitor.
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Affiliation(s)
- Yunliang Gao
- Department of Urology, the Second Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Mental Disorders, Changsha, China
- Hunan Clinical Research Center of Minimally Invasive Urology, Changsha, China
| | - Yuanyuan Tang
- Department of Oncology, the Second Xiangya Hospital, Central South University, Changsha, China.
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2
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Macwan RS, Ferrero G, Pardini B, Naccarati A, Kozlowski PB, Papetti MJ. TPM4 overexpression drives colon epithelial cell tumorigenesis by suppressing differentiation and promoting proliferation. Neoplasia 2025; 59:101093. [PMID: 39608123 PMCID: PMC11636349 DOI: 10.1016/j.neo.2024.101093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 11/11/2024] [Accepted: 11/18/2024] [Indexed: 11/30/2024]
Abstract
OBJECTIVE The high morbidity and mortality associated with colorectal cancer (CRC) and the recent increases in early-onset CRC obviate the need for novel methods to detect and treat this disease, particularly at early stages. We hypothesize that aberrant expression of genes involved in the crypt-luminal migration of colon epithelial cells, a process necessary for their growth arrest and maturation, may disrupt differentiation and transition cells from a normal to tumorigenic state. METHODS We searched for contractility- and motility-related genes that are dysregulated in human CRC relative to normal colon. RNA expression of one such gene, tropomyosin 4 (TPM4), was measured by qRT-PCR and RNA-seq in human colorectal tissues at various stages of tumorigenesis: CRC, adenoma, and at-risk (grossly normal mucosa from a patient with Familial Adenomatous Polyposis, or FAP), relative to controls. Effects of aberrant TPM4 expression on colon epithelial cell proliferation and maturation were determined by overexpression using stable transfection in spontaneously differentiating Caco2 cells or silencing using siRNA in proliferating cells. RESULTS TPM4 is overexpressed at various stages of tumorigenesis, including CRC, adenoma, and grossly normal FAP colon tissue, as well as in proliferating versus differentiating Caco2 cells. TPM4.2 overexpression in differentiating Caco2 cells markedly inhibits certain aspects of maturation, notably sucrase isomaltase and glutathione-S-transferase alpha1 expression, and causes morphological and cell junction abnormalities. Conversely, siRNA-mediated suppression of TPM4.2 inhibits Caco2 proliferation. CONCLUSIONS TPM4 overexpression attenuates colon epithelial cell differentiation and promotes proliferation. Therefore, TPM4 expression may be a biomarker to enhance strategies for CRC diagnosis and treatment.
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Affiliation(s)
| | - Giulio Ferrero
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; Department of Computer Science, University of Turin, Turin, Italy
| | - Barbara Pardini
- Italian Institute for Genomic Medicine (IIGM), c/o IRCCS Candiolo, Candiolo 10060, Turin, Italy; Candiolo Cancer Institute, FPO-IRCCS, Candiolo 10060, Turin, Italy
| | - Alessio Naccarati
- Italian Institute for Genomic Medicine (IIGM), c/o IRCCS Candiolo, Candiolo 10060, Turin, Italy; Candiolo Cancer Institute, FPO-IRCCS, Candiolo 10060, Turin, Italy
| | | | - Michael J Papetti
- Touro College of Pharmacy, New York, NY 10036, USA; Touro College of Osteopathic Medicine, New York, NY 10027, USA.
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3
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Sun C, Zhang K, Ni C, Wan J, Duan X, Lou X, Yao X, Li X, Wang M, Gu Z, Yang P, Li Z, Qin Z. Transgelin promotes lung cancer progression via activation of cancer-associated fibroblasts with enhanced IL-6 release. Oncogenesis 2023; 12:18. [PMID: 36990991 DOI: 10.1038/s41389-023-00463-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 03/09/2023] [Accepted: 03/10/2023] [Indexed: 03/31/2023] Open
Abstract
Cancer-associated fibroblasts (CAFs), the principal constituent of the heterogenous tumor microenvironment, have been shown to promote tumor progression; however, the underlying mechanism is still less clear. Here, we find that transgelin (TAGLN) protein levels increased in primary CAFs isolated from human lung cancer, compared with those in paired normal fibroblasts. Tumor microarrays (TMAs) revealed that increased stromal TAGLN levels correlates with more lymphatic metastasis of tumor cells. In a subcutaneous tumor transplantation model, overexpression of Tagln in fibroblasts also increased tumor cell spread in mice. Further experiments show that Tagln overexpression promoted fibroblast activation and mobility in vitro. And TAGLN facilitates p-p65 entry into the nucleus, thereby activating the NF-κB signaling pathway in fibroblasts. Activated fibroblasts promote lung cancer progression via enhancing the release of pro-inflammatory cytokines, especially interleukine-6 (IL-6). Our study revealed that the high levels of stromal TAGLN is a predictive risk factor for patients with lung cancer. Targeting stromal TAGLN may present an alternative therapeutic strategy against lung cancer progression.
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Affiliation(s)
- Chanjun Sun
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Kaishang Zhang
- Thoracic Surgery Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Chen Ni
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Jiajia Wan
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Xixi Duan
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Xiaohan Lou
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Xiaohan Yao
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Xiangnan Li
- Thoracic Surgery Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Ming Wang
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Zhuoyu Gu
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Pengyuan Yang
- Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 100101, Beijing, China
| | - Zhenzhen Li
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450052, Henan, China.
| | - Zhihai Qin
- Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450052, Henan, China.
- Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, No. 15 Datun Road, Chaoyang Area, 100101, Beijing, China.
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Stabenau KA, Samuels TL, Lam TK, Mathison AJ, Wells C, Altman KW, Battle MA, Johnston N. Pepsinogen/Proton Pump Co-Expression in Barrett's Esophageal Cells Induces Cancer-Associated Changes. Laryngoscope 2023; 133:59-69. [PMID: 35315085 DOI: 10.1002/lary.30109] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 02/27/2022] [Accepted: 03/04/2022] [Indexed: 02/02/2023]
Abstract
EDUCATIONAL OBJECTIVE At the conclusion of this presentation, participants should better understand the carcinogenic potential of pepsin and proton pump expression in Barrett's esophagus. OBJECTIVE Barrett's esophagus (BE) is a well-known risk factor for esophageal adenocarcinoma (EAC). Gastric H+ /K+ ATPase proton pump and pepsin expression has been demonstrated in some cases of BE; however, the contribution of local pepsin and proton pump expression to carcinogenesis is unknown. In this study, RNA sequencing was used to examine global transcriptomic changes in a BE cell line ectopically expressing pepsinogen and/or gastric H+ /K+ ATPase proton pumps. STUDY DESIGN In vitro translational. METHODS BAR-T, a human BE cell line devoid of expression of pepsinogen or proton pumps, was transduced by lentivirus-encoding pepsinogen (PGA5) and/or gastric proton pump subunits (ATP4A, ATP4B). Changes relative to the parental line were assessed by RNA sequencing. RESULTS Top canonical pathways associated with protein-coding genes differentially expressed in pepsinogen and/or proton pump expressing BAR-T cells included those involved in the tumor microenvironment and epithelial-mesenchymal transition. Top upstream regulators of coding transcripts included TGFB1 and ERBB2, which are associated with the pathogenesis and prognosis of BE and EAC. Top upstream regulators of noncoding transcripts included p300-CBP, I-BET-151, and CD93, which have previously described associations with EAC or carcinogenesis. The top associated disease of both coding and noncoding transcripts was cancer. CONCLUSIONS These data support the carcinogenic potential of pepsin and proton pump expression in BE and reveal molecular pathways affected by their expression. Further study is warranted to investigate the role of these pathways in carcinogenesis associated with BE. LEVEL OF EVIDENCE NA Laryngoscope, 133:59-69, 2023.
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Affiliation(s)
- Kaleigh A Stabenau
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Tina L Samuels
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Tina K Lam
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Angela J Mathison
- Genomic Sciences and Precision Medicine Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.,Division of Research, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Clive Wells
- Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Kenneth W Altman
- Department of Otolaryngology, Geisinger Health System, Danville, California, USA
| | - Michele A Battle
- Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Nikki Johnston
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.,Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
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Godefa TM, Derks S, Thijssen VLJL. Galectins in Esophageal Cancer: Current Knowledge and Future Perspectives. Cancers (Basel) 2022; 14:5790. [PMID: 36497271 PMCID: PMC9736038 DOI: 10.3390/cancers14235790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/18/2022] [Accepted: 11/22/2022] [Indexed: 11/27/2022] Open
Abstract
Esophageal cancer is a disease with poor overall survival. Despite advancements in therapeutic options, the treatment outcome of esophageal cancer patients remains dismal with an overall 5-year survival rate of approximately 20 percent. To improve treatment efficacy and patient survival, efforts are being made to identify the factors that underlie disease progression and that contribute to poor therapeutic responses. It has become clear that some of these factors reside in the tumor micro-environment. In particular, the tumor vasculature and the tumor immune micro-environment have been implicated in esophageal cancer progression and treatment response. Interestingly, galectins represent a family of glycan-binding proteins that has been linked to both tumor angiogenesis and tumor immunosuppression. Indeed, in several cancer types, galectins have been identified as diagnostic and/or prognostic markers. However, the role of galectins in esophageal cancer is still poorly understood. Here, we summarize the current literature with regard to the expression and potential functions of galectins in esophageal cancer. In addition, we highlight the gaps in the current knowledge and we propose directions for future research in order to reveal whether galectins contribute to esophageal cancer progression and provide opportunities to improve the treatment and survival of esophageal cancer patients.
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Affiliation(s)
- Tesfay M. Godefa
- Department of Medical Oncology, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
- Cancer Center Amsterdam, Cancer Biology & Immunology, De Boelelaan 1118, 1081 HV Amsterdam, The Netherlands
- Oncode Institute, Jaarbeursplein 6, 3521 AL Utrecht, The Netherlands
| | - Sarah Derks
- Department of Medical Oncology, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
- Cancer Center Amsterdam, Cancer Biology & Immunology, De Boelelaan 1118, 1081 HV Amsterdam, The Netherlands
- Oncode Institute, Jaarbeursplein 6, 3521 AL Utrecht, The Netherlands
| | - Victor L. J. L. Thijssen
- Cancer Center Amsterdam, Cancer Biology & Immunology, De Boelelaan 1118, 1081 HV Amsterdam, The Netherlands
- Radiation Oncology, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
- Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
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Liu QW, Ruan HJ, Chao WX, Li MX, Jiao YL, Ward DG, Gao SG, Qi YJ. N-linked glycoproteomic profiling in esophageal squamous cell carcinoma. World J Gastroenterol 2022; 28:3869-3885. [PMID: 36157541 PMCID: PMC9367225 DOI: 10.3748/wjg.v28.i29.3869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 04/26/2022] [Accepted: 07/06/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Mass spectrometry-based proteomics and glycomics reveal post-translational modifications providing significant biological insights beyond the scope of genomic sequencing.
AIM To characterize the N-linked glycoproteomic profile in esophageal squamous cell carcinoma (ESCC) via two complementary approaches.
METHODS Using tandem multilectin affinity chromatography for enrichment of N-linked glycoproteins, we performed N-linked glycoproteomic profiling in ESCC tissues by two-dimensional gel electrophoresis (2-DE)-based and isobaric tags for relative and absolute quantification (iTRAQ) labeling-based mass spectrometry quantitation in parallel, followed by validation of candidate glycoprotein biomarkers by Western blot.
RESULTS 2-DE-based and iTRAQ labeling-based quantitation identified 24 and 402 differentially expressed N-linked glycoproteins, respectively, with 15 in common, demonstrating the outperformance of iTRAQ labeling-based quantitation over 2-DE and complementarity of these two approaches. Proteomaps showed the distinct compositions of functional categories between proteins and glycoproteins with differential expression associated with ESCC. Western blot analysis validated the up-regulation of total procathepsin D and high-mannose procathepsin D, and the down-regulation of total haptoglobin, high-mannose clusterin, and GlcNAc/sialic acid-containing fraction of 14-3-3ζ in ESCC tissues. The serum levels of glycosylated fractions of clusterin, proline-arginine-rich end leucine-rich repeat protein, and haptoglobin in patients with ESCC were remarkably higher than those in healthy controls.
CONCLUSION Our study provides insights into the aberrant N-linked glycoproteome associated with ESCC, which will be a valuable resource for future investigations.
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Affiliation(s)
- Qi-Wei Liu
- Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment; Henan Key Laboratory of Cancer Epigenetics; Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471003, Henan Province, China
| | - Hao-Jie Ruan
- Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment; Henan Key Laboratory of Cancer Epigenetics; Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471003, Henan Province, China
| | - Wei-Xia Chao
- Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment; Henan Key Laboratory of Cancer Epigenetics; Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471003, Henan Province, China
| | - Meng-Xiang Li
- Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment; Henan Key Laboratory of Cancer Epigenetics; Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471003, Henan Province, China
| | - Ye-Lin Jiao
- Department of Pathology, The First People’s Hospital of Luo Yang, Luoyang 471000, Henan Province, China
| | - Douglas G Ward
- Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom
| | - She-Gan Gao
- Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment; Henan Key Laboratory of Cancer Epigenetics; Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471003, Henan Province, China
| | - Yi-Jun Qi
- Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment; Henan Key Laboratory of Cancer Epigenetics; Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471003, Henan Province, China
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Kim S, Kim GH, Park SJ, Kwon CH, I H, Lee MW, Lee BE. Exosomal MicroRNA Analyses in Esophageal Squamous Cell Carcinoma Cell Lines. J Clin Med 2022; 11:4426. [PMID: 35956043 PMCID: PMC9369365 DOI: 10.3390/jcm11154426] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 07/23/2022] [Accepted: 07/26/2022] [Indexed: 11/17/2022] Open
Abstract
Exosomal miRNAs have been studied in various cancers as minimally invasive biomarkers. This study aimed to investigate the potential of exosomal microRNAs (miRNAs) as biomarkers for esophageal squamous cell carcinoma (ESCC). Exosomes were isolated from cultures of esophageal epithelial cell and ESCC cell lines using ExoDisc, and exosomal miRNAs were detected via miRNA sequencing. Of the differentially expressed 14 miRNAs, the top 2 up-regulated miRNAs (miR-205-5p and miR-429) and top 2 down-regulated miRNAs (miR-375-3p and miR-483-3p) were selected as ESCC target miRNAs. Four selected exosomal miRNAs were validated in the plasma of 20 healthy controls (HCs) and 40 ESCC patients via quantitative reverse transcription-polymerase chain reaction. The expression of plasma exosomal miR-205-5p and miR-429 significantly increased, while that of plasma exosomal miR-375-3p was significantly reduced in ESCC patients compared to that in HCs. At cut-off values of 5.04, 2.564, and 0.136, the sensitivity and specificity for the diagnosis of ESCC were 72.5% and 70.0% for miR-205-5p, 60.0% and 60.0% for miR-429, and 65.0% and 65.0% for miR-375-3p, respectively. Based on the exosomal miRNAs identified in ESCC cell lines, our study demonstrated that plasma exosomal miR-205-5p, miR-429, and miR-375-3p could serve as potential biomarkers for ESCC diagnosis.
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Affiliation(s)
- Sora Kim
- Department of Convergence Medical Sciences, Graduate School of Medicine, Pusan National University, Yangsan 50612, Korea;
| | - Gwang Ha Kim
- Department of Internal Medicine, Pusan National University College of Medicine, Busan 49241, Korea; (M.W.L.); (B.E.L.)
- Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Korea; (S.J.P.); (C.H.K.)
| | - Su Jin Park
- Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Korea; (S.J.P.); (C.H.K.)
| | - Chae Hwa Kwon
- Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Korea; (S.J.P.); (C.H.K.)
| | - Hoseok I
- Department of Thoracic Surgery, Pusan National University College of Medicine, Busan 49241, Korea;
| | - Moon Won Lee
- Department of Internal Medicine, Pusan National University College of Medicine, Busan 49241, Korea; (M.W.L.); (B.E.L.)
| | - Bong Eun Lee
- Department of Internal Medicine, Pusan National University College of Medicine, Busan 49241, Korea; (M.W.L.); (B.E.L.)
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8
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Wang D, Chen J, Han J, Wang K, Fang W, Jin J, Xue S. iTRAQ and two-dimensional-LC-MS/MS reveal NAA10 is a potential biomarker in esophageal squamous cell carcinoma. Proteomics Clin Appl 2022; 16:e2100081. [PMID: 35182098 DOI: 10.1002/prca.202100081] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Revised: 01/24/2022] [Accepted: 02/15/2022] [Indexed: 01/03/2025]
Abstract
PURPOSE Esophageal squamous cell carcinoma (ESCC) is one of the most common and serious malignancies in China. However, the exact mechanisms of tumor progression are still unclear. Thus, identifying biomarkers for early diagnosis, prognostic and recurrence assessment of ESCC is necessary. EXPERIMENTAL DESIGN iTRAQ was used to identify differentially expressed proteins (DEPs) in tumor tissues. N-alpha-acetyltransferase 10 (NAA10) is confirmed and validated by immunohistochemistry and western blotting. Furthermore, the effects of NAA10 on TE-1 cells were detected by CCK-8, colonies formation, anchorage-independent growth in soft agar, migration and transwell assays. LinkedOmics was used to identify differential gene expression with NAA10 and to analyze Gene Ontology and KEGG pathways. Coexpression gene network was conducted by the STRING database and Cytoscape software (MCODE plug-in). RESULTS 516 DEPs were identified. NAA10 was downregulated in cancer tissues and selected for further confirmed. Furthermore, NAA10 can inhibit proliferation and tumorigenesis, and suppress migration and invasion of TE-1. Functional network analysis suggested that NAA10 regulates the ribosome pathways involving eight ribosomal proteins. CONCLUSION AND CLINICAL RELEVANCE These findings clearly demonstrated that NAA10 is a tumor suppressor and novel potential biomarker for ESCC, laying a foundation for further study of the role of NAA10 in carcinogenesis.
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Affiliation(s)
- Dong Wang
- Department of General Surgery (Emergency Surgery), Fujian Medical University Union Hospital, Fujian, China
| | - Jinyan Chen
- Institute for Immunology, Fujian Academy of Medical Sciences, Fuzhou, Fujian, China
- Fujian Provincial Key Laboratory of Medical Analysis, Fuzhou, Fujian, China
| | - Junyong Han
- Institute for Immunology, Fujian Academy of Medical Sciences, Fuzhou, Fujian, China
- Fujian Provincial Key Laboratory of Medical Analysis, Fuzhou, Fujian, China
| | - Kun Wang
- Institute for Immunology, Fujian Academy of Medical Sciences, Fuzhou, Fujian, China
- Fujian Provincial Key Laboratory of Medical Analysis, Fuzhou, Fujian, China
| | - Weimin Fang
- Fujian Provincial Cancer Hospital, Fuzhou, Fujian, China
| | - Jingjun Jin
- Institute for Immunology, Fujian Academy of Medical Sciences, Fuzhou, Fujian, China
- Fujian Provincial Key Laboratory of Medical Analysis, Fuzhou, Fujian, China
| | - Shijie Xue
- Institute for Immunology, Fujian Academy of Medical Sciences, Fuzhou, Fujian, China
- Fujian Provincial Key Laboratory of Medical Analysis, Fuzhou, Fujian, China
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9
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Pan X, Wang J, Guo L, Na F, Du J, Chen X, Zhong A, Zhao L, Zhang L, Zhang M, Wan X, Wang M, Liu H, Dai S, Tan P, Chen J, Liu Y, Hu B, Chen C. Identifying a confused cell identity for esophageal squamous cell carcinoma. Signal Transduct Target Ther 2022; 7:122. [PMID: 35418165 PMCID: PMC9008022 DOI: 10.1038/s41392-022-00946-8] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 02/25/2022] [Accepted: 03/01/2022] [Indexed: 02/07/2023] Open
Abstract
The cell identity of malignant cells and how they acquire it are fundamental for our understanding of cancer. Here, we report that esophageal squamous cell carcinoma (ESCC) cells display molecular features equally similar but distinct to all three types of normal esophageal epithelial cells, which we term as confused cell identity (CCI). CCI is an independent prognostic marker associated with poor prognosis in ESCC. Further, we identify tropomyosin 4 (TPM4) as a critical CCI gene that promotes the aggressiveness of ESCC in vitro and in vivo. And TPM4 creates CCI through activating the Jak/STAT-SOX2 pathway. Thus, our study suggests an unrecognized feature of ESCC cells, which might be of value for clinic prognosis and potential interference.
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Affiliation(s)
- Xiangyu Pan
- Department of Gastroenterology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jian Wang
- Department of Gastroenterology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Linjie Guo
- Department of Gastroenterology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Feifei Na
- Department of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Jiajia Du
- Department of Gastroenterology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xuelan Chen
- Department of Gastroenterology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Ailing Zhong
- Department of Gastroenterology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Lei Zhao
- Department of Gastroenterology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Lu Zhang
- Department of Gastroenterology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Mengsha Zhang
- Department of Gastroenterology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xudong Wan
- Department of Gastroenterology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Manli Wang
- Department of Gastroenterology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Hongyu Liu
- Department of Gastroenterology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Siqi Dai
- Department of Gastroenterology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Ping Tan
- Dpartment of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Jingyao Chen
- Department of Gastroenterology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yu Liu
- Department of Gastroenterology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
| | - Bing Hu
- Department of Gastroenterology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
| | - Chong Chen
- Department of Gastroenterology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
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10
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Zhou X, Zhu X, Yao J, Wang X, Wang N. Comprehensive analysis of clinical prognosis and molecular immune characterization of tropomyosin 4 in pancreatic cancer. Invest New Drugs 2021; 39:1469-1483. [PMID: 33983530 DOI: 10.1007/s10637-021-01128-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 05/05/2021] [Indexed: 11/26/2022]
Abstract
Pancreatic cancer (PC) is one of the most lethal human solid malignancies with devastating prognosis, making biomarker detection considerably important. Immune infiltrates in microenvironment is associated with patients' survival in PC. The role of Tropomyosin 4 (TPM4) gene in PC has not been reported. Our study first identifies TPM4 expression and its potential biological functions in PC. The potential oncogenic roles of TPM4 was examined using the datasets of TCGA (The cancer genome atlas) and GEO (Gene expression omnibus). We investigated the clinical significance and prognostic value of TPM4 gene based on The Gene Expression Profiling Interactive Analysis (GEPIA) and survival analysis. TIMER and TISIDB databases were used to analyze the correlations between TPM4 gene and tumor-infiltrating immune cells. We found that the expression level of TPM4 was upregulated in PC malignant tissues with the corresponding normal tissues as controls. High TPM4 expression was correlated with the worse clinicopathological features and poor prognosis in PC cohorts. The positive association between TPM4 expression and tumor-infiltrating immune cells was identified in tumor microenvironment (TME). Moreover, functional enrichment analysis suggested that TPM4 might participate in cell adhesion and promote tumor cell migration. This is the first comprehensive study to disclose that TPM4 may serve as a novel prognostic biomarker associating with immune infiltrates and provide a potential therapeutic target for the treatment of PC.
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Affiliation(s)
- Xue Zhou
- Department of Nephrology, Tianjin Haihe Hospital, Tianjin, 300350, China
| | - Xiaowei Zhu
- Tianjin Third Central Hospital, 83 Jintang Road, Hedong District, Tianjin, 300170, China
| | - Junchao Yao
- Department of Hepatobiliary Surgery, Tianjin Third Central Hospital, Tianjin, 300170, China
| | - Xue Wang
- Department of Respiratory Medicine, Tianjin Third Central Hospital, Tianjin, 300170, China
| | - Ning Wang
- Tianjin Third Central Hospital, 83 Jintang Road, Hedong District, Tianjin, 300170, China.
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11
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Dagamajalu S, Vijayakumar M, Shetty R, Rex DAB, Narayana Kotimoole C, Prasad TSK. Proteogenomic examination of esophageal squamous cell carcinoma (ESCC): new lines of inquiry. Expert Rev Proteomics 2020; 17:649-662. [PMID: 33151123 DOI: 10.1080/14789450.2020.1845146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Introduction: Esophageal squamous cell carcinoma (ESCC), a histopathologic subtype of esophageal cancer is a major cause of cancer-related morbidity and mortality worldwide. This is primarily because patients are diagnosed at an advanced stage by the time symptoms appear. The genomics and mass spectrometry-based proteomics continue to provide important leads toward biomarker discovery for ESCC. However, such leads are yet to be translated into clinical utilities. Areas covered: We gathered information pertaining to proteomics and proteogenomics efforts in ESCC from the literature search until 2020. An overview of omics approaches to discover the candidate biomarkers for ESCC were highlighted. We present a summary of recent investigations of alterations in the level of gene and protein expression observed in biological samples including body fluids, tissue/biopsy and in vitro-based models. Expert opinion: A large number of protein-based biomarkers and therapeutic targets are being used in cancer therapy. Several candidates are being developed as diagnostics and prognostics for the management of cancers. High-resolution proteomic and proteogenomic approaches offer an efficient way to identify additional candidate biomarkers for diagnosis, monitoring of disease progression, prediction of response to chemo and radiotherapy. Some of these biomarkers can also be developed as therapeutic targets.
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Affiliation(s)
- Shobha Dagamajalu
- Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to Be University) , Mangalore, India
| | - Manavalan Vijayakumar
- Department of Surgical Oncology, Yenepoya Medical College, Yenepoya (Deemed to Be University) , Mangalore, India
| | - Rohan Shetty
- Department of Surgical Oncology, Yenepoya Medical College, Yenepoya (Deemed to Be University) , Mangalore, India
| | - D A B Rex
- Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to Be University) , Mangalore, India
| | - Chinmaya Narayana Kotimoole
- Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to Be University) , Mangalore, India
| | - T S Keshava Prasad
- Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to Be University) , Mangalore, India
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12
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Chen Q, Li J, Yang X, Ma J, Gong F, Liu Y. Prdx1 promotes the loss of primary cilia in esophageal squamous cell carcinoma. BMC Cancer 2020; 20:372. [PMID: 32357862 PMCID: PMC7195802 DOI: 10.1186/s12885-020-06898-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Accepted: 04/23/2020] [Indexed: 12/16/2022] Open
Abstract
Background Loss of primary cilia is frequently observed in tumor cells, suggesting that the absence of this organelle may promote tumorigenesis through aberrant signal transduction, the inability to exit the cell cycle, and promotion of tumor cell invasion. Primary cilia loss also occurs in esophageal squamous cell carcinoma (ESCC) cells, but the molecular mechanisms that explain how ESCC cells lose primary cilia remain poorly understood. Methods Inhibiting the expression of Prdx1 in the ESCC cells to detect the up-regulated genes related to cilium regeneration and down-regulated genes related to cilium disassembly by Gene chip. And, mice and cell experiments were carried to confirm the role of the HEF1-Aurora A-HDAC6 signaling axis in ESCC. Results In this study, we found that silencing Peroxiredoxin 1 (Prdx1) restores primary cilia formation, and over-expressing Prdx1 induces primary cilia loss in ESCC cells. We also showed that the expression of Prdx1 regulates the action of the HEF1-Aurora A-HDAC6 signaling axis to promote the disassembly of primary cilia, and suppression of Prdx1 results in decreased tumor formation and tumor mass volume in vivo. Conclusions These results suggest that Prdx1 is a novel regulator of primary cilia formation in ESCC cells.
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Affiliation(s)
- Qiongzhen Chen
- College of Life and Environmental Science, Wenzhou University, Wenzhou, China
| | - Jinmeng Li
- School of Pharmacy, Wenzhou Medical University, Wenzhou, China
| | - Xiaoning Yang
- School of Pharmacy, Wenzhou Medical University, Wenzhou, China
| | - Junfeng Ma
- School of Pharmacy, Wenzhou Medical University, Wenzhou, China
| | - Fanghua Gong
- School of Pharmacy, Wenzhou Medical University, Wenzhou, China.
| | - Yu Liu
- The first affiliated hospital of Wenzhou Medical University, Wenzhou, China.
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13
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Abstract
Mass spectrometry-based proteomics analysis could categorize proteins and study their interactions in large scale in human cancers. By this method, many proteins are upregulated or downregulated in esophageal squamous cell carcinoma (ESCC) when compared to nonneoplastic esophageal mucosae. The method can also be used to identify novel, effective biomarkers for early diagnosis or predict prognosis of patients with ESCC. These changes are associated with different clinical and pathological parameters. Different biological matrices such as pathological tissue, body fluids, and cancer cell lines-based proteomics have widely been used. Herein, we described cell line-based label-free shotgun proteomics (in-solution tryptic digestion) to identify the protein biomarkers differently expressed in ESCC.
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14
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Chen Z, He S, Zhan Y, He A, Fang D, Gong Y, Li X, Zhou L. TGF-β-induced transgelin promotes bladder cancer metastasis by regulating epithelial-mesenchymal transition and invadopodia formation. EBioMedicine 2019; 47:208-220. [PMID: 31420300 PMCID: PMC6796540 DOI: 10.1016/j.ebiom.2019.08.012] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Revised: 07/29/2019] [Accepted: 08/05/2019] [Indexed: 12/24/2022] Open
Abstract
Background Metastatic bladder cancer (BLCA) is a lethal disease with an unmet need for study. Transgelin (TAGLN) is an actin-binding protein that affects the dynamics of the actin cytoskeleton indicating its robust potential as a metastasis initiator. Here, we sought to explore the expression pattern of TAGLN and elucidate its specific functioning and mechanisms in BLCA. Methods A comprehensive assessment of TAGLN expression in BLCA was performed in three cohorts with a total of 847 patients. The potential effects of TAGLN on BLCA were further determined using clinical genomic analyses that guided the subsequent functional and mechanistic studies. In vitro migration, invasion assays and in vivo metastatic mouse model were performed to explore the biological functions of TAGLN in BLCA cells. Immunofluorescence, western blot and correlation analysis were used to investigate the molecular mechanisms of TAGLN. Findings TAGLN was highly expressed in BLCA and correlated with advanced prognostic features. TAGLN promoted cell colony formation and cell migration and invasion both in vitro and in vivo by inducing invadopodia formation and epithelial-mesenchymal transition, during which a significant correlation between TAGLN and Slug was observed. The progression-dependent correlation between TGF-β and TAGLN was analysed at both the cellular and tissue levels, while TGF-β-mediated migration was abolished by the suppression of TAGLN. Interpretation Overall, TAGLN is a promising novel prognosis biomarker of BLCA, and its metastatic mechanisms indicate that TAGLN may represent a novel target agent that can be utilized for the clinical management of invasive and metastatic BLCA. Fund This work was supported by the National Natural Science Foundation of China [81772703, 81672546, 81602253]; the Natural Science Foundation of Beijing [71772219, 7152146]. and Innovative Fund for Doctoral Students of Peking University Health Science Center (BUM2018BSS002). Funders had no role in the design of the study, data collection, data analysis, interpretation, or the writing of this report.
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Affiliation(s)
- Zhicong Chen
- Department of Urology, Peking University First Hospital, Beijing 100034, China; Institute of Urology, Peking University, Beijing 100034, China; National Urological Cancer Center, Beijing 100034, China; Beijing Key Laboratory of Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing 100034, China
| | - Shiming He
- Department of Urology, Peking University First Hospital, Beijing 100034, China; Institute of Urology, Peking University, Beijing 100034, China; National Urological Cancer Center, Beijing 100034, China; Beijing Key Laboratory of Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing 100034, China
| | - Yonghao Zhan
- Department of Urology, Peking University First Hospital, Beijing 100034, China; Institute of Urology, Peking University, Beijing 100034, China; National Urological Cancer Center, Beijing 100034, China; Beijing Key Laboratory of Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing 100034, China; Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 45000, China
| | - Anbang He
- Department of Urology, Peking University First Hospital, Beijing 100034, China; Institute of Urology, Peking University, Beijing 100034, China; National Urological Cancer Center, Beijing 100034, China; Beijing Key Laboratory of Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing 100034, China
| | - Dong Fang
- Department of Urology, Peking University First Hospital, Beijing 100034, China; Institute of Urology, Peking University, Beijing 100034, China; National Urological Cancer Center, Beijing 100034, China; Beijing Key Laboratory of Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing 100034, China
| | - Yanqing Gong
- Department of Urology, Peking University First Hospital, Beijing 100034, China; Institute of Urology, Peking University, Beijing 100034, China; National Urological Cancer Center, Beijing 100034, China; Beijing Key Laboratory of Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing 100034, China.
| | - Xuesong Li
- Department of Urology, Peking University First Hospital, Beijing 100034, China; Institute of Urology, Peking University, Beijing 100034, China; National Urological Cancer Center, Beijing 100034, China; Beijing Key Laboratory of Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing 100034, China.
| | - Liqun Zhou
- Department of Urology, Peking University First Hospital, Beijing 100034, China; Institute of Urology, Peking University, Beijing 100034, China; National Urological Cancer Center, Beijing 100034, China; Beijing Key Laboratory of Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing 100034, China.
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15
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Zhao X, Jiang M, Wang Z. TPM4 promotes cell migration by modulating F-actin formation in lung cancer. Onco Targets Ther 2019; 12:4055-4063. [PMID: 31239699 PMCID: PMC6554522 DOI: 10.2147/ott.s198542] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Accepted: 04/08/2019] [Indexed: 12/29/2022] Open
Abstract
Background: Tropomyosin 4 (TPM4) is a member of the tropomyosin family of actin-binding proteins. Abnormal level of TPM4 is found in several cancers, and TPM4 is considered as a potential detecting marker for ovarian cancer, breast cancer, colon cancer, keratoacanthoma and esophageal squamous cell carcinoma. In this paper, the function of TPM4 in lung cancer cell lines was determined. Materials and methods: TPM4 knockout cells were constructed by CRISPR/CAS9 technique. TPM4 overexpression cells were also constructed based on TPM4 knockout cells. Cell growth ability was detected by MTS assay. The potency of cell motility was investigated using transwell assay and wound scratch assay. The protein levels in lung cancer cells were determined by western-blot. Immunofluorescence technique was used to image the structure of F-actin. Results: As a result, TPM4 downregulation and TPM4 upregulation cell models were obtained successfully. Cell motility was inhibited by the suppression of TPM4 while cell migration was enhanced in TPM4 upregulated cells. But TPM4 was not involved in cell proliferation and EMT progression. Microfilaments were depolymerized result from the suppression of TPM4 expression. And F-actin assembly was increased when TPM4 was upregulated. Conclusion: In summary, TPM4 was able to promote cell motility by altering the actin cytoskeleton directly.
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Affiliation(s)
- Xiaoting Zhao
- Department of Cellular and Molecular Biology, Beijing Chest Hospital, Capital Medical University /Beijing Tuberculosis and Thoracic Tumor Research Institute, Tongzhou, Beijing, People's Republic of China
| | - Mei Jiang
- Department of Cellular and Molecular Biology, Beijing Chest Hospital, Capital Medical University /Beijing Tuberculosis and Thoracic Tumor Research Institute, Tongzhou, Beijing, People's Republic of China
| | - Ziyu Wang
- Department of Cellular and Molecular Biology, Beijing Chest Hospital, Capital Medical University /Beijing Tuberculosis and Thoracic Tumor Research Institute, Tongzhou, Beijing, People's Republic of China
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16
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Zhu Y, Qi X, Yu C, Yu S, Zhang C, Zhang Y, Liu X, Xu Y, Yang C, Jiang W, Tian G, Li X, Bergquist J, Zhang J, Wang L, Mi J. Identification of prothymosin alpha (PTMA) as a biomarker for esophageal squamous cell carcinoma (ESCC) by label-free quantitative proteomics and Quantitative Dot Blot (QDB). Clin Proteomics 2019; 16:12. [PMID: 30988666 PMCID: PMC6449931 DOI: 10.1186/s12014-019-9232-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Accepted: 03/25/2019] [Indexed: 12/12/2022] Open
Abstract
Background Esophageal cancer (EC) is one of the malignant tumors with a poor prognosis. The early stage of EC is asymptomatic, so identification of cancer biomarkers is important for early detection and clinical practice. Methods In this study, we compared the protein expression profiles in esophageal squamous cell carcinoma (ESCC) tissues and adjacent normal esophageal tissues from five patients through high-resolution label-free mass spectrometry. Through bioinformatics analysis, we found the differentially expressed proteins of ESCC. To perform the rapid identification of biomarkers, we adopted a high-throughput protein identification technique of Quantitative Dot Blot (QDB). Meanwhile, the QDB results were verified by classical immunohistochemistry. Results In total 2297 proteins were identified, out of which 308 proteins were differentially expressed between ESCC tissues and normal tissues. By bioinformatics analysis, the four up-regulated proteins (PTMA, PAK2, PPP1CA, HMGB2) and the five down-regulated proteins (Caveolin, Integrin beta-1, Collagen alpha-2(VI), Leiomodin-1 and Vinculin) were selected and validated in ESCC by Western Blot. Furthermore, we performed the QDB and IHC analysis in 64 patients and 117 patients, respectively. The PTMA expression was up-regulated gradually along the progression of ESCC, and the PTMA expression ratio between tumor and adjacent normal tissue was significantly increased along with the progression. Therefore, we suggest that PTMA might be a potential candidate biomarker for ESCC. Conclusion In this study, label-free quantitative proteomics combined with QDB revealed that PTMA expression was up-regulated in ESCC tissues, and PTMA might be a potential candidate for ESCC. Since Western Blot cannot achieve rapid and high-throughput screening of mass spectrometry results, the emergence of QDB meets this demand and provides an effective method for the identification of biomarkers.
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Affiliation(s)
- Yanping Zhu
- 1Precision Medicine Research Center, Binzhou Medical University, No. 346 Guanhai Rd., Laishan District, Yantai, 264003 Shandong Province People's Republic of China
| | - Xiaoying Qi
- 1Precision Medicine Research Center, Binzhou Medical University, No. 346 Guanhai Rd., Laishan District, Yantai, 264003 Shandong Province People's Republic of China
| | - Cuicui Yu
- Department of Anesthesiology, The Affiliated Yantai Yuhuangding Hospital of Qing Dao University, No. 20 Yudong Rd., Zhifu District, Yantai, S264009 Shandong People's Republic of China
| | - Shoujun Yu
- 3Department of Ultrasound, Yantai Affiliated Hospital of Binzhou Medical University, No. 717 Jinfu Rd., Muping District, Binzhou, 264100 Shandong Province People's Republic of China
| | - Chao Zhang
- 1Precision Medicine Research Center, Binzhou Medical University, No. 346 Guanhai Rd., Laishan District, Yantai, 264003 Shandong Province People's Republic of China
| | - Yuan Zhang
- 1Precision Medicine Research Center, Binzhou Medical University, No. 346 Guanhai Rd., Laishan District, Yantai, 264003 Shandong Province People's Republic of China
| | - Xiuxiu Liu
- 1Precision Medicine Research Center, Binzhou Medical University, No. 346 Guanhai Rd., Laishan District, Yantai, 264003 Shandong Province People's Republic of China
| | - Yuxue Xu
- 1Precision Medicine Research Center, Binzhou Medical University, No. 346 Guanhai Rd., Laishan District, Yantai, 264003 Shandong Province People's Republic of China
| | - Chunhua Yang
- 1Precision Medicine Research Center, Binzhou Medical University, No. 346 Guanhai Rd., Laishan District, Yantai, 264003 Shandong Province People's Republic of China
| | - Wenguo Jiang
- 1Precision Medicine Research Center, Binzhou Medical University, No. 346 Guanhai Rd., Laishan District, Yantai, 264003 Shandong Province People's Republic of China
| | - Geng Tian
- 1Precision Medicine Research Center, Binzhou Medical University, No. 346 Guanhai Rd., Laishan District, Yantai, 264003 Shandong Province People's Republic of China
| | - Xuri Li
- 4State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060 People's Republic of China
| | - Jonas Bergquist
- 1Precision Medicine Research Center, Binzhou Medical University, No. 346 Guanhai Rd., Laishan District, Yantai, 264003 Shandong Province People's Republic of China.,5Department of Chemistry, BMC, Uppsala University, PO Box 599, Husargatan 3, 75124 Uppsala, Sweden
| | - Jiandi Zhang
- 1Precision Medicine Research Center, Binzhou Medical University, No. 346 Guanhai Rd., Laishan District, Yantai, 264003 Shandong Province People's Republic of China.,Yantai Zestern Biotechnique Co. LTD, 39 Keji Ave. Bioasis, Yantai, People's Republic of China
| | - Lei Wang
- 7Department of Thoracic Surgery, The First Affiliated Hospital of Harbin Medical University, No. 23, Youzheng Street, Nangang District, Harbin, 150000 Heilongjiang Province People's Republic of China
| | - Jia Mi
- 1Precision Medicine Research Center, Binzhou Medical University, No. 346 Guanhai Rd., Laishan District, Yantai, 264003 Shandong Province People's Republic of China
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17
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Xie B, Lin J, Sui K, Huang Z, Chen Z, Hang W. Differential diagnosis of multielements in cancerous and non-cancerous esophageal tissues. Talanta 2018; 196:585-591. [PMID: 30683409 DOI: 10.1016/j.talanta.2018.12.061] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Revised: 12/05/2018] [Accepted: 12/21/2018] [Indexed: 12/31/2022]
Abstract
It is known that variations in the concentrations of certain elements in humans may be an indication of cancers. In this work, a method for the quantitative analysis of 22 elements in non-tumor and esophageal squamous cell carcinoma (ESCC) tissues from the same individual is reported. Based on the optimized platform combined with multivariate analysis, diagnostic models of ESCC were established using principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), showing excellent classification of cancerous and non-cancerous group by metallomic profiling. Elemental concentrations of 10 elements (Mn, Se, Cu, Ti, Mg, Fe, Co, Zn, Sr, Ca) showed significant difference (p < 0.001) in tumor and non-tumor tissues, in which Mn, Se, Cu and Ti are the top 4 elements of statistical significance and a shift towards higher concentration levels has also been observed in the tumor samples. These results confirm the considerable potential of elemental studies for biomedical purposes. To our knowledge, previous studies on elemental concentration in esophageal cancer were performed in serum or plasma levels; and this is the first study to evaluate the association of tissue elemental concentrations with ESCC.
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Affiliation(s)
- Binbin Xie
- Department of Chemistry and the MOE Key Lab of Spectrochemical Analysis & Instrumentation, College of Chemistry and Chemical Engineering, State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen 361005, Fujian, China
| | - Jianqing Lin
- Department of Surgical Oncology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian, China
| | - Ke Sui
- Department of Chemistry and the MOE Key Lab of Spectrochemical Analysis & Instrumentation, College of Chemistry and Chemical Engineering, State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen 361005, Fujian, China
| | - Zhijun Huang
- Department of Surgical Oncology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian, China
| | - Zhiyao Chen
- Department of Surgical Oncology, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian, China.
| | - Wei Hang
- Department of Chemistry and the MOE Key Lab of Spectrochemical Analysis & Instrumentation, College of Chemistry and Chemical Engineering, State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen 361005, Fujian, China.
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18
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Khowal S, Naqvi SH, Monga S, Jain SK, Wajid S. Assessment of cellular and serum proteome from tongue squamous cell carcinoma patient lacking addictive proclivities for tobacco, betel nut, and alcohol: Case study. J Cell Biochem 2018; 119:5186-5221. [PMID: 29236289 DOI: 10.1002/jcb.26554] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2017] [Accepted: 11/30/2017] [Indexed: 02/06/2023]
Abstract
The intriguing molecular pathways involved in oral carcinogenesis are still ambiguous. The oral squamous cell carcinoma (OSCC) ranks as the most common type constituting more than 90% of the globally diagnosed oral cancers cases. The elevation in the OSCC incidence rate during past 10 years has an alarming impression on human healthcare. The major challenges associated with OSCC include delayed diagnosis, high metastatic rates, and low 5-year survival rates. The present work foundations on reverse genetic strategy and involves the identification of genes showing expressional variability in an OSCC case lacking addictive proclivities for tobacco, betel nut, and/or alcohol, major etiologies. The expression modulations in the identified genes were analyzed in 16 patients comprising oral pre-cancer and cancer histo-pathologies. The genes SCCA1 and KRT1 were found to down regulate while DNAJC13, GIPC2, MRPL17, IG-Vreg, SSFA2, and UPF0415 upregulated in the oral pre-cancer and cancer pathologies, implicating the genes as crucial players in oral carcinogenesis.
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Affiliation(s)
- Sapna Khowal
- Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, India
| | - Samar H Naqvi
- Molecular Diagnostics, Genetix Biotech Asia (P) Ltd., New Delhi, India
| | - Seema Monga
- Department of ENT, Hamdard Institute of Medical Sciences and Research, Jamia Hamdard, New Delhi, India
| | - Swatantra K Jain
- Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, India
- Department of Biochemistry, Hamdard Institute of Medical Sciences and Research, Jamia Hamdard, New Delhi, India
| | - Saima Wajid
- Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, India
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19
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The clinical significance and biological function of tropomyosin 4 in colon cancer. Biomed Pharmacother 2018; 101:1-7. [PMID: 29455030 DOI: 10.1016/j.biopha.2018.01.166] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2018] [Revised: 01/31/2018] [Accepted: 01/31/2018] [Indexed: 01/06/2023] Open
Abstract
Tropomyosin 4 (TPM4) has been found to be dys-regulated, and function as oncogene or anti-oncogene in human cancers. However, there was no report on the clinical significance and biological function of TPM4 in colon cancer. This study was designed to investigate the clinical value and biological function of TPM4 in colon cancer. Thus, we detected the TPM4 expression in colon cancer clinical samples, and conducted the gain-of-function in colon cancer cell lines. In our results, TPM4 mRNA and protein expressions were reduced in colon cancer tissues and cell lines compared with normal colon tissues and colon epithelial cell line, respectively. TPM4 protein low-expression was obviously associated with clinical stage, T classification (invasion depth), N classification (lymph node metastasis), distant metastasis and differentiation. Survival analysis showed low-expression of TPM4 was an unfavorable independent prognostic factor for colon cancer patients. Moreover, the experiments in vitro suggested up-regulated TPM4 expression suppressed colon cancer cell migration, invasion and metastasis-associated gene expression including MMP-2, MMP-9 and MT1-MMP, but had no effect on cell proliferation. In conclusion, TPM4 is associated with clinical progression in colon cancer patient and acts as a tumor suppressor in colon cancer cell.
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20
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Heawchaiyaphum C, Pientong C, Phusingha P, Vatanasapt P, Promthet S, Daduang J, Teeramatwanich W, Kongyingyoes B, Chuerduangphui J, Ekalaksananan T. Peroxiredoxin-2 and zinc-alpha-2-glycoprotein as potentially combined novel salivary biomarkers for early detection of oral squamous cell carcinoma using proteomic approaches. J Proteomics 2017; 173:52-61. [PMID: 29199150 DOI: 10.1016/j.jprot.2017.11.022] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2017] [Revised: 10/20/2017] [Accepted: 11/27/2017] [Indexed: 01/07/2023]
Abstract
No effective screening method is available for oral squamous cell carcinoma (OSCC) that is recognized to influence by environmental factors as well as human papillomavirus (HPV) and Epstein-Barr virus (EBV). Therefore, we sought to identify salivary biomarkers for screening of OSCC with or without HPV and/or EBV infection. Saliva, lesion and oral exfoliated cells were collected from OSCC patients and cancer-free controls (CFCs) and grouped depending on their HPV- and EBV-infection status. Salivary protein was precipitated and subjected to 2-dimensional gel electrophoresis. Differential expression of proteins was identified by mass spectrometry and validated by Western blotting. Distinctive expression patterns of salivary proteins were detected in OSCC as compared with CFCs. Levels of peroxiredoxin-2 (PRDX-2) and zinc-alpha-2-glycoprotein (ZAG) were significantly up-regulated in OSCC cases (p<0.001) relative to CFCs. Similarly, these proteins were also up-regulated in lesion cells compared with oral exfoliated cells (p<0.001). However, the expression patterns of these proteins were not significantly influenced by patient histories (risk factors). In combination, these proteins yielded the highest discriminatory power (AUC=0.999), sensitivity (100%), and specificity (98.77%) in distinguishing the early stages of OSCC. The detection of PRDX-2 combining with ZAG protein could potentially be used as salivary biomarkers for early screening of OSCC. SIGNIFICANCE Our findings demonstrate a useful of combined detection of PRDX-2 and ZAG as a salivary biomarker for the early detection of OSCC.
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Affiliation(s)
- Chukkris Heawchaiyaphum
- Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand
| | - Chamsai Pientong
- Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.
| | - Pensiri Phusingha
- Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand
| | - Patravoot Vatanasapt
- Department of Otorhinolaryngology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.
| | - Supannee Promthet
- Department of Epidemiology, Faculty of Public Health, Khon Kaen University, Khon Kaen, Thailand; HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.
| | - Jureerut Daduang
- Department of Clinical Chemistry, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand; HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.
| | - Watchareporn Teeramatwanich
- Department of Otorhinolaryngology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand
| | - Bunkerd Kongyingyoes
- Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
| | - Jureeporn Chuerduangphui
- Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand
| | - Tipaya Ekalaksananan
- Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.
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21
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Zhang J, Zhi C, Zhen F, Yuan X, Jiao C, Zhu H, Zhu H, Feng Y. iTRAQ-Based Quantitative Proteomic Analyses of High Grade Esophageal Squamous Intraepithelial Neoplasia. Proteomics Clin Appl 2017; 11. [PMID: 28816019 DOI: 10.1002/prca.201600167] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2016] [Revised: 07/18/2017] [Indexed: 01/08/2023]
Abstract
Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and is the fourth most lethal cancer in China. Little is known about the proteome of high grade esophageal squamous intraepithelial neoplasia (HGN), which is a premalignant lesion of ESCC. A quantitative proteomic analysis using an isobaric tag for relative and absolute quantification (iTRAQ) approach is used to characterize the protein expression profiles in HGN. Among the 3156 identified proteins, a total of 236 proteins are discovered to be differentially expressed. Compared with paired normal esophageal epithelial tissues, 138 proteins are upregulated and 98 proteins are downregulated in HGN. Bioinformatics analyses are performed according to gene ontology, clusters of orthologous groups, and kyoto encyclopedia of genes and genomes enrichment analyses. Six differentially expressed proteins are chosen and validated by Western blotting. The results of the study increase our understanding of early tumorigenesis during ESCC, and provide insights into the proteome at the initial stages of the disease that can be used to identify potential biomarkers for early diagnosis and for therapeutic targets.
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Affiliation(s)
- Jingjing Zhang
- State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Jiangning, Nanjing, China.,Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, China
| | - Chunchun Zhi
- Department of Anatomy, Nanjing Medical University, Jiangning, Nanjing, China
| | - Fuxi Zhen
- Department of Cardio-thoracic Surgery, First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Xiaoqin Yuan
- Department of Anatomy, Nanjing Medical University, Jiangning, Nanjing, China
| | - Chunhua Jiao
- Department of Gastroenterology, First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Hong Zhu
- Department of Gastroenterology, First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Hui Zhu
- State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Jiangning, Nanjing, China
| | - Yadong Feng
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, China.,Previously Department of Gastroenterology, First Affiliated Hospital with Nanjing Medical University, Nanjing, China
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22
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Shi XJ, Ding L, Zhou W, Ji Y, Wang J, Wang H, Ma Y, Jiang G, Tang K, Ke Y, Zhao W, Liu HM. Pro-Apoptotic Effects of JDA-202, a Novel Natural Diterpenoid, on Esophageal Cancer Through Targeting Peroxiredoxin I. Antioxid Redox Signal 2017; 27:73-92. [PMID: 27650197 PMCID: PMC5510680 DOI: 10.1089/ars.2016.6703] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
AIMS Esophageal cancer (EC) is an aggressive malignancy and the most common solid tumor of gastrointestinal tract all over the world, with high incidence in Asia. The current study was designed to investigate the anticancer efficacy and mechanism that is involved in the action of a natural ent-kaurene diterpenoid, JDA-202, targeting EC. RESULTS We found that an antioxidant protein peroxiredoxin I (Prx I) was upregulated in human EC tissues as well as in EC cell lines. JDA-202, a novel natural compound isolated from Isodon rubescens (Labiatae), was proved to possess strong anti-proliferative activities on those cell lines. Importantly, JDA-202 does not only bind to Prx I directly and markedly inhibit the activity of Prx I in vitro, but it also significantly induces hydrogen peroxide (H2O2)-related cell death. Furthermore, overexpression of Prx I significantly reversed EC109 cell apoptosis caused by JDA-202, whereas short interfering RNA (siRNA)-induced Prx I knockdown resulted in marked cell death even without JDA-202 pretreatment. On the other hand, the increased phosphorylation of mitogen-activated protein kinase (MAPK) proteins (c-Jun N-terminal kinase [JNK], p38, and extracellular signal-regulated kinase [ERK]) by JDA-202 was suppressed by N-acetylcysteine (NAC) or catalase, a known reactive oxygen species (ROS) or H2O2 scavenger. JDA-202 also significantly inhibited the growth of EC109 tumor xenograft, without significant body weight loss and multi-organ toxicities. Innovation and Conclusion: Our findings, for the first time, demonstrated that JDA-202 may serve as a lead compound, targeting the overexpressed Prx I in EC cell lines and ROS accumulation as well as inhibiting the activation of their downstream targets in MAPKs. Antioxid. Redox Signal. 27, 73-92.
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Affiliation(s)
- Xiao-Jing Shi
- Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-Innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou, China
| | - Lina Ding
- Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-Innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou, China
| | - Wenjuan Zhou
- Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-Innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou, China
| | - Yage Ji
- Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-Innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou, China
| | - Junwei Wang
- Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-Innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou, China
| | - Huimin Wang
- Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-Innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou, China
| | - Yongcheng Ma
- Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-Innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou, China
| | - Guozhong Jiang
- Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-Innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou, China
| | - Kai Tang
- Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-Innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou, China
| | - Yu Ke
- Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-Innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou, China
| | - Wen Zhao
- Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-Innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou, China
| | - Hong-Min Liu
- Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-Innovation Center of Henan Province for New Drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou, China
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23
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Xi HQ, Zhang KC, Li JY, Cui JX, Zhao P, Chen L. Expression and clinicopathologic significance of TUFM and p53 for the normal-adenoma-carcinoma sequence in colorectal epithelia. World J Surg Oncol 2017; 15:90. [PMID: 28449687 PMCID: PMC5408486 DOI: 10.1186/s12957-017-1111-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2016] [Accepted: 02/01/2017] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Evidence indicates that most cases of colorectal carcinoma (CRC) develop from adenoma. A previous study demonstrated that mitochondrial Tu translation elongation factor (TUFM) might serve as an independent prognostic factor for colorectal cancer. However, the expression and function of TUFM in the normal-adenoma-cancer sequence have not been reported. In this study, we investigated the clinicopathologic significance of TUFM and p53 expression for the normal-adenoma-carcinoma sequence in colorectal epithelia and evaluated the roles of TUFM during the progression of colorectal tumors. METHODS Paraffin-embedded specimens from 261 colorectal normal mucosa samples, 157 adenomas, and 104 early carcinomas were analyzed for TUFM and p53 expression by immunohistochemistry. RESULTS Expression of TUFM and p53 was significantly increased during the colorectal normal-adenoma-carcinoma sequence (all P < 0.05). The expression of TUFM and p53 was associated with histologic type of adenomas (P = 0.028; P = 0.001) and grade of dysplasia (all P = 0.001). Expression of TUFM was positively correlated with that of p53 (r = 0.319, P = 0.001). CONCLUSIONS Upregulated TUFM expression may play an important role in the transformation from colorectal normal mucosa to carcinoma through adenoma. Combined immunohistochemical detection of TUFM and p53 may be useful for evaluating the biological behavior of colorectal adenoma.
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Affiliation(s)
- Hong-Qing Xi
- Department of General Surgery, Chinese People's Liberation Army General Hospital, 100853, Beijing, China
| | - Ke-Cheng Zhang
- Department of General Surgery, Chinese People's Liberation Army General Hospital, 100853, Beijing, China
| | - Ji-Yang Li
- Department of General Surgery, Chinese People's Liberation Army General Hospital, 100853, Beijing, China
| | - Jian-Xin Cui
- Department of General Surgery, Chinese People's Liberation Army General Hospital, 100853, Beijing, China
| | - Po Zhao
- Department of Pathology, Chinese People's Liberation Army General Hospital, 100853, Beijing, China.
| | - Lin Chen
- Department of General Surgery, Chinese People's Liberation Army General Hospital, 100853, Beijing, China.
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Yazdian-Robati R, Ahmadi H, Riahi MM, Lari P, Aledavood SA, Rashedinia M, Abnous K, Ramezani M. Comparative proteome analysis of human esophageal cancer and adjacent normal tissues. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2017; 20:265-271. [PMID: 28392898 PMCID: PMC5378963 DOI: 10.22038/ijbms.2017.8354] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Objective(s): Ranking as the sixth commonest cancer, esophageal squamous cell carcinoma (ESCC) represents one of the leading causes of cancer death worldwide. One of the main reasons for the low survival of patients with esophageal cancer is its late diagnosis. Materials and Methods: We used proteomics approach to analyze ESCC tissues with the aim of a better understanding of the malignant mechanism and searching candidate protein biomarkers for early diagnosis of esophageal cancer. The differential protein expression between cancerous and normal esophageal tissues was investigated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Then proteins were identified by matrix-assisted laser desorption/ ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS) and MASCOT web based search engine. Results: We reported 4 differentially expressed proteins involved in the pathological process of esophageal cancer, such as annexinA1 (ANXA1), peroxiredoxin-2 (PRDX2), transgelin (TAGLN) andactin-aortic smooth muscle (ACTA2). Conclusion: In this report we have introduced new potential biomarker (ACTA2). Moreover, our data confirmed some already known markers for EC in our region.
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Affiliation(s)
- Rezvan Yazdian-Robati
- Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Homa Ahmadi
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maryam Matbou Riahi
- Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Parisa Lari
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Amir Aledavood
- Cancer Research Center, Department of Radiation oncology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Marzieh Rashedinia
- Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Iran
| | - Khalil Abnous
- Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Ramezani
- Nanotechnology Research Center, Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad Iran
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25
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Fassan M, Realdon S, Vianello L, Quarta S, Ruol A, Castoro C, Scarpa M, Zaninotto G, Guzzardo V, Sileni VC, Pontisso P, Rugge M. Squamous cell carcinoma antigen (SCCA) is up-regulated during Barrett's carcinogenesis and predicts esophageal adenocarcinoma resistance to neoadjuvant chemotherapy. Oncotarget 2017; 8:24372-24379. [PMID: 28042960 PMCID: PMC5421854 DOI: 10.18632/oncotarget.14108] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Accepted: 11/22/2016] [Indexed: 12/15/2022] Open
Abstract
Squamous Cell Carcinoma Antigen (SCCA) is consistently overexpressed in many different solid tumors, and has been associated with both tumor aggressiveness and chemoresistance. No data, however, is currently available on SCCA expression during esophageal Barrett's carcinogenesis, nor on SCCA expression's role on esophageal adenocarcinoma chemoresistance. The SCCA immunohistochemical expression was assessed in a series of 100 biopsy samples covering the whole histological spectrum of Barrett's oncogenesis. Squamous native mucosa was characterized by a moderate to strong cytoplasmic and nuclear SCCA expression in suprabasal, medium, and superficial layers. On the other hand, almost half of the considered lesions did not express SCCA; the other half featured weak to moderate SCCA expression. The relationship between SCCA protein expression and tumor response to neoadjuvant chemotherapy was assessed in 90 esophageal adenocarcinoma specimens (40 biopsy and 50 surgery specimens), stratified according to Mandard tumor regression grade. As observed in other settings, the presence of SCCA expression clustered in the group of tumors characterized by a lower responsiveness to neoadjuvant treatments. The present results suggest an involvement of SCCA in a subset of Barrett-related tumors, and prompt to consider the SCCA-protein expression as response-predictive marker of neoadjuvant therapy in esophageal adenocarcinomas.
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Affiliation(s)
- Matteo Fassan
- Department of Medicine (DIMED), Surgical Pathology Unit, University of Padua, Padua, Italy
| | - Stefano Realdon
- Gastroenterology Unit, Istituto Oncologico Veneto, IOV-IRCCS, Padua, Italy
| | - Luca Vianello
- Department of Medicine (DIMED), Surgical Pathology Unit, University of Padua, Padua, Italy
| | - Santina Quarta
- Department of Medicine (DIMED), 5th Medical Clinic, University of Padua, Padua, Italy
| | - Alberto Ruol
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), 3rd Surgical Clinic, University of Padua, Padua, Italy
| | - Carlo Castoro
- Esophageal and Digestive Tract Surgical Unit, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy
| | - Marco Scarpa
- Esophageal and Digestive Tract Surgical Unit, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy
| | - Giovanni Zaninotto
- Imperial College London, Department of Surgery and Cancer, Division of Surgery, London, UK
| | - Vincenza Guzzardo
- Department of Medicine (DIMED), Surgical Pathology Unit, University of Padua, Padua, Italy
| | - Vanna Chiarion Sileni
- Melanoma & Esophageal Oncology Unit, Istituto Oncologico Veneto, IOV-IRCCS, Padua, Italy
| | - Patrizia Pontisso
- Department of Medicine (DIMED), 5th Medical Clinic, University of Padua, Padua, Italy
| | - Massimo Rugge
- Department of Medicine (DIMED), Surgical Pathology Unit, University of Padua, Padua, Italy
- Veneto Tumour Registry, Veneto Region, Padua, Italy
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Guo JH, Xing GL, Fang XH, Wu HF, Zhang B, Yu JZ, Fan ZM, Wang LD. Proteomic profiling of fetal esophageal epithelium, esophageal cancer, and tumor-adjacent esophageal epithelium and immunohistochemical characterization of a representative differential protein, PRX6. World J Gastroenterol 2017; 23:1434-1442. [PMID: 28293090 PMCID: PMC5330828 DOI: 10.3748/wjg.v23.i8.1434] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Revised: 11/21/2016] [Accepted: 12/08/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To understand the molecular mechanism of esophageal cancer development and provide molecular markers for screening high-risk populations and early diagnosis.
METHODS Two-dimensional electrophoresis combined with mass spectrometry were adopted to screen differentially expressed proteins in nine cases of fetal esophageal epithelium, eight cases of esophageal cancer, and eight cases of tumor-adjacent normal esophageal epithelium collected from fetuses of different gestational age, or esophageal cancer patients from a high-risk area of esophageal cancer in China. Immunohistochemistry (avidin-biotin-horseradish peroxidase complex method) was used to detect the expression of peroxiredoxin (PRX)6 in 91 cases of esophageal cancer, tumor-adjacent normal esophageal tissue, basal cell hyperplasia, dysplasia, and carcinoma in situ, as well as 65 cases of esophageal epithelium from fetuses at a gestational age of 3-9 mo.
RESULTS After peptide mass fingerprint analysis and search of protein databases, 21 differential proteins were identified; some of which represent a protein isoform. Varying degrees of expression of PRX6 protein, which was localized mainly in the cytoplasm, were detected in adult and fetal normal esophageal tissues, precancerous lesions, and esophageal cancer. With the progression of esophageal lesions, PRX6 protein expression showed a declining trend (P < 0.05). In fetal epithelium from fetuses at gestational age 3-6 mo, PRX6 protein expression showed a declining trend with age (P < 0.05). PRX6 protein expression was significantly higher in well-differentiated esophageal cancer tissues than in poorly differentiated esophageal cancer tissues (P < 0.05).
CONCLUSION Development and progression of esophageal cancer result from interactions of genetic changes (accumulation or superposition). PRX6 protein is associated with fetal esophageal development and cancer differentiation.
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Pan H, Gu L, Liu B, Li Y, Wang Y, Bai X, Li L, Wang B, Peng Q, Yao Z, Tang Z. Tropomyosin-1 acts as a potential tumor suppressor in human oral squamous cell carcinoma. PLoS One 2017; 12:e0168900. [PMID: 28182650 PMCID: PMC5300227 DOI: 10.1371/journal.pone.0168900] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2016] [Accepted: 12/05/2016] [Indexed: 01/16/2023] Open
Abstract
It is widely accepted that oral squamous cell carcinoma (OSCC) is a major contributor to the incidence and mortality of neck and head cancer. Tropomyosin-1 (TPM1), which is expressed at a low level, has been considered a prominent tumor-suppressing gene in a variety of solid tumors, although the precise mechanism of the TPM1 gene in OSCC progression remains unknown. We found that TPM1 expression levels decreased in OSCC patients and OSCC cell lines. The overall and cancer-specific survival of patients who exhibited low TPM1 levels were inferior to those of patients who had high TPM1 levels. It was also found that OSCC patients who suffered from disease stageⅠ-Ⅱ were more likely to have an up-regulated TPM1 expression level, and OSCC patients with lymph node metastasis had a higher probability of exhibiting reduced TPM1 expression. We show that overexpression of TPM1 can promote cell apoptosis and inhibit migration. Our results suggest that TPM1 can suppress tumors in OSCC, and the TPM1 expression level is related to OSCC patient prognosis.
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Affiliation(s)
- Hao Pan
- Department of Oral & Maxillofacial Surgery, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, China
| | - Liqun Gu
- Department of Oral & Maxillofacial Surgery, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, China
| | - Binjie Liu
- Department of Periodontics, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, China
| | - Yiping Li
- Department of Prosthodontics, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, China
| | - Yuehong Wang
- Department of Prosthodontics, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, China
| | - Xinna Bai
- Department of Conservative Dentistry & Endodontics, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, China
| | - Long Li
- Department of Oral Pathology, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, China
| | - Baisheng Wang
- Department of Oral & Maxillofacial Surgery, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, China
| | - Qian Peng
- Department of Oral & Maxillofacial Surgery, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, China
| | - Zhigang Yao
- Department of Oral Pathology, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, China
| | - Zhangui Tang
- Department of Oral & Maxillofacial Surgery, Xiangya Stomatological Hospital & School of Stomatology, Central South University, Changsha, Hunan, China
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Dahiya K, Dhankhar R. Updated overview of current biomarkers in head and neck carcinoma. World J Methodol 2016; 6:77-86. [PMID: 27018324 PMCID: PMC4804254 DOI: 10.5662/wjm.v6.i1.77] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2015] [Revised: 01/20/2016] [Accepted: 03/07/2016] [Indexed: 02/06/2023] Open
Abstract
Squamous cell cancer is the most common type of malignancy arising from the epithelial cells of the head and neck region. Head and neck squamous cell carcinoma (HNSCC) is one of the predominant causes of cancer related casualties worldwide. Overall prognosis in this disease has improved to some extent with the advancements in therapeutic modalities but detection of primary tumor at its initial stage and prevention of relapse are the major targets to be achieved for further improvement in terms of survival rate of patients. Latest achievements in basic research regarding molecular characterization of the disease has helped in better perception of the molecular mechanisms involved in HNSCC progression and also in recognizing and targeting various molecular biomarkers associated with HNSCC. In the present article, we review the information regarding latest and potential biomarkers for the early detection of HNSCC. A detailed molecular characterization, ultimately, is likely to improve the development of new therapeutic strategies, potentially relevant to diagnosis and prognosis of head and neck cancers. The need for more accurate and timely disease prediction has generated enormous research interests in this field.
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Yang YJ, Baek JY, Goo J, Shin Y, Park JK, Jang JY, Wang SB, Jeong W, Lee HJ, Um HD, Lee SK, Choi Y, Rhee SG, Chang TS. Effective Killing of Cancer Cells Through ROS-Mediated Mechanisms by AMRI-59 Targeting Peroxiredoxin I. Antioxid Redox Signal 2016; 24:453-69. [PMID: 26528922 DOI: 10.1089/ars.2014.6187] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
AIMS The intrinsic increase of reactive oxygen species (ROS) production in cancer cells after malignant transformation frequently induces redox adaptation, leading to enhanced antioxidant capacity. Peroxiredoxin I (PrxI), an enzyme responsible for eliminating hydrogen peroxide, has been found to be elevated in many types of cancer cells. Since overexpression of PrxI promoted cancer cells' survival and resistance to chemotherapy and radiotherapy, PrxI has been proposed as a therapeutic target for anticancer drugs. In this study, we aimed to investigate the anticancer efficacy of a small molecule inhibitor of PrxI. RESULTS By a high-throughput screening approach, we identified AMRI-59 as a potent inhibitor of PrxI. AMRI-59 increased cellular ROS, leading to the activation of both mitochondria- and apoptosis signal-regulated kinase-1-mediated signaling pathways, resulting in apoptosis of A549 human lung adenocarcinoma. AMRI-59 caused no significant changes in ROS level, proliferation, and apoptosis of PrxI-knockdown A549 cells by RNA interference. PrxI overexpression or N-acetylcysteine pretreatment abrogated AMRI-59-induced cytotoxicity in A549 cells. AMRI-59 rendered tumorigenic ovarian cells more susceptible to ROS-mediated death compared with nontumorigenic cells. Moreover, significant antitumor activity of AMRI-59 was observed in mouse tumor xenograft model implanted with A549 cells with no apparent acute toxicity. INNOVATION This study offers preclinical proof-of-concept for AMRI-59, a lead small molecule inhibitor of PrxI, as an anticancer agent. CONCLUSIONS Our results highlight a promising strategy for cancer therapy that preferentially eradicates cancer cells by targeting the PrxI-mediated redox-dependent survival pathways.
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Affiliation(s)
- Yeon Ju Yang
- 1 Graduate School of Pharmaceutical Sciences, Ewha Womans University , Seoul, Republic of Korea.,2 Brain Korea 21 PLUS Project for Medical Science, Yonsei University , Seoul, Republic of Korea
| | - Jin Young Baek
- 1 Graduate School of Pharmaceutical Sciences, Ewha Womans University , Seoul, Republic of Korea
| | - Jail Goo
- 3 College of Life Sciences and Biotechnology, Korea University , Seoul, Republic of Korea
| | - Yoonho Shin
- 4 College of Pharmacy, Seoul National University , Seoul, Republic of Korea
| | - Jong Kuk Park
- 5 Laboratory of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences , Seoul, Republic of Korea
| | - Ji Yong Jang
- 1 Graduate School of Pharmaceutical Sciences, Ewha Womans University , Seoul, Republic of Korea
| | - Su Bin Wang
- 1 Graduate School of Pharmaceutical Sciences, Ewha Womans University , Seoul, Republic of Korea
| | - Woojin Jeong
- 6 Division of Life Sciences, Ewha Womans University , Seoul, Republic of Korea
| | - Hwa Jeong Lee
- 1 Graduate School of Pharmaceutical Sciences, Ewha Womans University , Seoul, Republic of Korea.,7 College of Pharmacy, Ewha Womans University , Seoul, Republic of Korea
| | - Hong-Duck Um
- 5 Laboratory of Radiation Cancer Biology, Korea Institute of Radiological and Medical Sciences , Seoul, Republic of Korea
| | - Sang Kook Lee
- 4 College of Pharmacy, Seoul National University , Seoul, Republic of Korea
| | - Yongseok Choi
- 3 College of Life Sciences and Biotechnology, Korea University , Seoul, Republic of Korea
| | - Sue Goo Rhee
- 8 Yonsei Biomedical Research Institute, Yonsei University College of Medicine , Seoul, Republic of Korea
| | - Tong-Shin Chang
- 1 Graduate School of Pharmaceutical Sciences, Ewha Womans University , Seoul, Republic of Korea.,7 College of Pharmacy, Ewha Womans University , Seoul, Republic of Korea
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Brücher BLDM, Li Y, Schnabel P, Daumer M, Wallace TJ, Kube R, Zilberstein B, Steele S, Voskuil JLA, Jamall IS. Genomics, microRNA, epigenetics, and proteomics for future diagnosis, treatment and monitoring response in upper GI cancers. Clin Transl Med 2016; 5:13. [PMID: 27053248 PMCID: PMC4823224 DOI: 10.1186/s40169-016-0093-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2016] [Accepted: 03/29/2016] [Indexed: 12/15/2022] Open
Abstract
One major objective for our evolving understanding in the treatment of cancers will be to address how a combination of diagnosis and treatment strategies can be used to integrate patient and tumor variables with an outcome-oriented approach. Such an approach, in a multimodal therapy setting, could identify those patients (1) who should undergo a defined treatment (personalized therapy) (2) in whom modifications of the multimodal therapy due to observed responses might lead to an improvement of the response and/or prognosis (individualized therapy), (3) who might not benefit from a particular toxic treatment regimen, and (4) who could be identified early on and thereby be spared the morbidity associated with such treatments. These strategies could lead in the direction of precision medicine and there is hope of integrating translational molecular data to improve cancer classifications. In order to achieve these goals, it is necessary to understand the key issues in different aspects of biotechnology to anticipate future directions of personalized and individualized diagnosis and multimodal treatment strategies. Providing an overview of translational data in cancers proved to be a challenge as different methods and techniques used to obtain molecular data are used and studies are based on different tumor entities with different tumor biology and prognoses as well as vastly different therapeutic approaches. The pros and cons of the available methodologies and the potential response data in genomics, microRNA, epigenetics and proteomics with a focus on upper gastrointestinal cancers are considered herein to allow for an understanding of where these technologies stand with respect to cancer diagnosis, prognosis and treatment.
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Affiliation(s)
- Björn L. D. M. Brücher
- />Theodor-Billroth-Academy®, Munich, Germany
- />Theodor-Billroth-Academy®, Sacramento, CA USA
- />INCORE, International Consortium of Research Excellence of the Theodor-Billroth-Academy®, Munich, Germany
- />INCORE, International Consortium of Research Excellence of the Theodor-Billroth-Academy®, Sacramento, CA USA
- />Bon Secours Cancer Institute, Richmond, VA USA
- />Department of Surgery, Carl-Thiem-Klinikum, Cottbus, Germany
| | - Yan Li
- />Proteogenomics Research Institute for Systems Medicine, San Diego, CA USA
| | - Philipp Schnabel
- />Institute of Pathology, University of Homburg Saar, Homburg, Germany
| | - Martin Daumer
- />Theodor-Billroth-Academy®, Munich, Germany
- />Theodor-Billroth-Academy®, Sacramento, CA USA
- />INCORE, International Consortium of Research Excellence of the Theodor-Billroth-Academy®, Munich, Germany
- />INCORE, International Consortium of Research Excellence of the Theodor-Billroth-Academy®, Sacramento, CA USA
- />Sylvia Lawry Center for MS Research, Munich, Germany
| | | | - Rainer Kube
- />Department of Surgery, Carl-Thiem-Klinikum, Cottbus, Germany
| | | | - Scott Steele
- />Case Western Reserve University, Cleveland, OH USA
- />Department of Surgery, Madigan Army Medical Center, Tacoma, WA USA
| | | | - Ijaz S. Jamall
- />Theodor-Billroth-Academy®, Munich, Germany
- />Theodor-Billroth-Academy®, Sacramento, CA USA
- />INCORE, International Consortium of Research Excellence of the Theodor-Billroth-Academy®, Munich, Germany
- />INCORE, International Consortium of Research Excellence of the Theodor-Billroth-Academy®, Sacramento, CA USA
- />Risk-Based Decisions, Inc., Sacramento, CA USA
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Zhou HM, Fang YY, Weinberger PM, Ding LL, Cowell JK, Hudson FZ, Ren M, Lee JR, Chen QK, Su H, Dynan WS, Lin Y. Transgelin increases metastatic potential of colorectal cancer cells in vivo and alters expression of genes involved in cell motility. BMC Cancer 2016; 16:55. [PMID: 26847345 PMCID: PMC4741053 DOI: 10.1186/s12885-016-2105-8] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Accepted: 01/31/2016] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND Transgelin is an actin-binding protein that promotes motility in normal cells. Although the role of transgelin in cancer is controversial, a number of studies have shown that elevated levels correlate with aggressive tumor behavior, advanced stage, and poor prognosis. Here we sought to determine the role of transgelin more directly by determining whether experimental manipulation of transgelin levels in colorectal cancer (CRC) cells led to changes in metastatic potential in vivo. METHODS Isogenic CRC cell lines that differ in transgelin expression were characterized using in vitro assays of growth and invasiveness and a mouse tail vein assay of experimental metastasis. Downstream effects of transgelin overexpression were investigated by gene expression profiling and quantitative PCR. RESULTS Stable overexpression of transgelin in RKO cells, which have low endogenous levels, led to increased invasiveness, growth at low density, and growth in soft agar. Overexpression also led to an increase in the number and size of lung metastases in the mouse tail vein injection model. Similarly, attenuation of transgelin expression in HCT116 cells, which have high endogenous levels, decreased metastases in the same model. Investigation of mRNA expression patterns showed that transgelin overexpression altered the levels of approximately 250 other transcripts, with over-representation of genes that affect function of actin or other cytoskeletal proteins. Changes included increases in HOOK1, SDCCAG8, ENAH/Mena, and TNS1 and decreases in EMB, BCL11B, and PTPRD. CONCLUSIONS Increases or decreases in transgelin levels have reciprocal effects on tumor cell behavior, with higher expression promoting metastasis. Chronic overexpression influences steady-state levels of mRNAs for metastasis-related genes.
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Affiliation(s)
- Hui-min Zhou
- />Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120 China
- />Department of Gastroenterology and Hepatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120 China
- />Department of Gastroenterology and Hepatology, The First Affiliated Hospital, School of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, 510000 China
| | - Yuan-yuan Fang
- />Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120 China
- />Department of Gastroenterology and Hepatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120 China
| | - Paul M. Weinberger
- />Center for Biotechnology and Genomic Medicine, Georgia Regents University, Augusta, GA 30912 USA
- />GRU Cancer Center, Georgia Regents University, Augusta, GA USA
| | - Ling-ling Ding
- />Department of Anatomy, Wu Han University, Wuhan, China
| | - John K. Cowell
- />GRU Cancer Center, Georgia Regents University, Augusta, GA USA
| | - Farlyn Z. Hudson
- />Institute of Molecular Medicine and Genetics, Georgia Regents University, Augusta, GA USA
| | - Mingqiang Ren
- />GRU Cancer Center, Georgia Regents University, Augusta, GA USA
| | - Jeffrey R. Lee
- />Department of Pathology, Georgia Regents University, and Charlie Norwood Veterans Affairs Medical Center, Augusta, GA USA
| | - Qi-kui Chen
- />Department of Gastroenterology and Hepatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120 China
| | - Hong Su
- />Department of Gastroenterology and Hepatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120 China
| | - William S. Dynan
- />Institute of Molecular Medicine and Genetics, Georgia Regents University, Augusta, GA USA
- />Departments of Radiation Oncology and Biochemistry, Emory University, Atlanta, GA USA
| | - Ying Lin
- />Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120 China
- />Department of Gastroenterology and Hepatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120 China
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Farid SG, Morris-Stiff G. "OMICS" technologies and their role in foregut primary malignancies. Curr Probl Surg 2015; 52:409-41. [PMID: 26527526 DOI: 10.1067/j.cpsurg.2015.08.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2014] [Accepted: 08/03/2015] [Indexed: 12/18/2022]
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Mishra M, Jiang H, Wu L, Chawsheen HA, Wei Q. The sulfiredoxin-peroxiredoxin (Srx-Prx) axis in cell signal transduction and cancer development. Cancer Lett 2015; 366:150-9. [PMID: 26170166 DOI: 10.1016/j.canlet.2015.07.002] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2015] [Revised: 05/06/2015] [Accepted: 07/04/2015] [Indexed: 12/13/2022]
Abstract
Redox signaling is a critical component of cell signaling pathways that are involved in the regulation of cell growth, metabolism, hormone signaling, immune regulation and variety of other physiological functions. Peroxiredoxin (Prx) is a family of thiol-based peroxidase that acts as a regulator of redox signaling. Members of Prx family can act as antioxidants and chaperones. Sulfiredoxin (Srx) is an antioxidant protein that exclusively reduces over-oxidized typical 2-Cys Prx. Srx has different affinities for individual Prx and it also catalyzes the deglutathionylation of variety of substrates. Individual component of the Srx-Prx system plays critical role in carcinogenesis by modulating cell signaling pathways involved in cell proliferation, migration and metastasis. Expression levels of individual component of the Srx-Prx axis have been correlated with patient survival outcome in multiple cancer types. This review will summarize the molecular basis of differences in the affinity of Srx for individual Prx and the role of individual component of the Srx-Prx system in tumor progression and metastasis. This enhanced understanding of molecular aspects of Srx-Prx interaction and its role in cell signal transduction will help define the Srx-Prx system as a future therapeutic target in human cancer.
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Affiliation(s)
- Murli Mishra
- Department of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, KY 40536, USA
| | - Hong Jiang
- Department of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, KY 40536, USA
| | - Lisha Wu
- Department of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, KY 40536, USA
| | - Hedy A Chawsheen
- Department of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, KY 40536, USA
| | - Qiou Wei
- Department of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, KY 40536, USA; Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
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Identification of Differential Protein Expression in Hepatocellular Carcinoma Induced Wistar Albino Rats by 2D Electrophoresis and MALDI-TOF-MS Analysis. Indian J Clin Biochem 2015; 31:194-202. [PMID: 27069327 DOI: 10.1007/s12291-015-0510-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Accepted: 05/13/2015] [Indexed: 12/12/2022]
Abstract
Hepato cellular carcinoma (HCC) is a type of malignant tumor. To investigate the proteins in cancer molecular mechanism and its role in HCC, we have used proteomic tools such as 2DE and MALDI-TOF-MS. Our investigation ravels that, plasma α-fetoprotein and carcinoembryonic antigen levels were elevated in DEN induced rats and gradually decreased after the treatment with 1,3BPMU. 2DE and MALDI-TOF-MS tool offers to identify the up and down regulation of proteins in HCC. Proteomic study reveals that, five differentially expressed proteins were identified in DEN induced rats and 1,3BPMU treated rats i.e. three up regulated protein such as T kininogen, NDPKB, PRMT1 (DEN induced rats), RGS19 and PAF (1,3BPMU treated rats) in 3BPMU treated rats, activation of transcription of a single gene from multiple promoters provides flexibility in the controlled gene expression. The regulations of hepatocyte stimulating factor were slow down the proliferation of hepatic cell and uncontrolled hepatic cell growth and also molecular signals strongly argue for a patho-physiological role in liver metastasis to control the cell aggression. This indicates that, anti cancer property of 1,3BPMU can be used as potent anti cancer agent. The present study also shows the proteomic approach helps to elucidate the tumor maker as well as regulatory marker proteins in HCC.
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Abstract
OBJECTIVE The aim of this study was to investigate the role of peroxiredoxin 1 (Prdx1) in the invasiveness of pancreatic ductal adenocarcinoma (PDAC) cells. METHODS Immunohistochemistry was used to determine overexpression of Prdx1 in human PDAC tissues. Immunoprecipitation and immunocytochemistry were used to determine the interaction and intracellular distribution of Prdx1 and a member of the mitogen-activated protein kinase (MAPK) family protein, p38 MAPK, in PDAC cells. Finally, immunocytochemistry and Matrigel invasion assay were used to examine the effects of Prdx1 and p38 MAPK on the formation of cell protrusions and PDAC cell invasion. RESULTS Prdx1 is overexpressed in human PDAC tissues. Peroxiredoxin 1 interacts with active forms of p38 MAPK, and complexes of Prdx1 and phosphorylated p38 MAPK localize at the leading edges of migrating PDAC cells. Suppression of Prdx1 decreases active p38 MAPK localized in cell protrusions and inhibits the invasiveness of PDAC cells. Consequently, suppression of Prdx1 inhibits membrane ruffling and protrusions. The p38 MAPK inhibitor SB203580 also decreases the formation of membrane protrusions and inhibits invasiveness. CONCLUSIONS Prdx1 associates with the formation of membrane protrusions through modulation of the activity of p38 MAPK, which in turn promotes PDAC cell invasion.
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Chen J, Kwong DL, Cao T, Hu Q, Zhang L, Ming X, Chen J, Fu L, Guan X. Esophageal squamous cell carcinoma (ESCC): advance in genomics and molecular genetics. Dis Esophagus 2015; 28:84-9. [PMID: 23796192 DOI: 10.1111/dote.12088] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Esophageal cancer is aggressive and has poor prognosis. Esophageal squamous cell carcinoma (ESCC) is histologically the most prevalent type of esophageal cancer and ranked as the sixth leading cause of cancer death worldwide. In recent years, cancer has been widely regarded as genetic disease, as well as epigenetic abnormalities including DNA methylation, histone deacetylation, chromatin remodeling, gene imprinting and noncoding RNA regulation. In this review, we will provide a general overview of genes, proteins and microRNAs that are involved in the development of ESCC, which aims to enhance our understanding of molecular mechanisms implicated in ESCC development and progression.
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Affiliation(s)
- J Chen
- Departments of Clinical Oncology, The University of Hong Kong, Hong Kong; Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Qi YJ, Ward DG, Pang C, Wang QM, Wei W, Ma J, Zhang J, Lou Q, Shimwell NJ, Martin A, Wong N, Chao WX, Wang M, Ma YF, Johnson PJ. Proteomic profiling of N-linked glycoproteins identifies ConA-binding procathepsin D as a novel serum biomarker for hepatocellular carcinoma. Proteomics 2014; 14:186-95. [PMID: 24259486 DOI: 10.1002/pmic.201300226] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2013] [Revised: 10/02/2013] [Accepted: 11/07/2013] [Indexed: 01/13/2023]
Abstract
The aim of this study was to identify novel biomarkers for the diagnosis of, and potential therapeutic targets for, hepatocellular carcinoma (HCC). Multilectin affinity chromatography was used to enrich N-linked glycoproteins from nontumorous liver and HCC tissues followed by 2DE and protein identification by MS. Twenty-eight differentially expressed proteins were identified. Western blotting validated consistently lower concentrations of human liver carboxylesterase 1 and haptoglobin, and higher concentration of procathepsin D (pCD) in HCC tissues. Knockdown of cathepsin D (CD) expression mediated by siRNA significantly inhibited the in vitro invasion of two HCC cell lines, SNU449 and SNU473, which normally secrete high-levels of CD. Prefractionation using individual lectins demonstrated an elevation in ConA-binding glycoforms of proCD and CD in HCC tissues. In the serum of HCC patients, "ConA-binding proCD" (ConA-pCD) is significantly increased in concentration and this increase is comprised of several distinct upregulated acidic isoforms (pI 4.5-5.5). Receiver operating characteristic analysis showed that the sensitivity and specificity of serum ConA-pCD for HCC diagnosis were 85% and 80%, respectively. This is the first report that serum ConA-pCD is increased significantly in HCC and is potentially useful as a serological biomarker for diagnosis of HCC.
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Affiliation(s)
- Yi-Jun Qi
- Key Laboratory of Cellular and Molecular Immunology, College of Medicine, Henan University, Kaifeng, P. R. China
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Zhang Y, Chen Y, Yu J, Liu G, Huang Z. Integrated transcriptome analysis reveals miRNA–mRNA crosstalk in laryngeal squamous cell carcinoma. Genomics 2014; 104:249-56. [DOI: 10.1016/j.ygeno.2014.06.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Revised: 06/19/2014] [Accepted: 06/23/2014] [Indexed: 11/26/2022]
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Uemura N, Kondo T. Current advances in esophageal cancer proteomics. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS 2014; 1854:687-95. [PMID: 25233958 DOI: 10.1016/j.bbapap.2014.09.011] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/04/2014] [Revised: 09/04/2014] [Accepted: 09/09/2014] [Indexed: 12/20/2022]
Abstract
We review the current status of proteomics for esophageal cancer (EC) from a clinician's viewpoint. The ultimate goal of cancer proteomics is the improvement of clinical outcome. The proteome as a functional translation of the genome is a straightforward representation of genomic mechanisms that trigger carcinogenesis. Cancer proteomics has identified the mechanisms of carcinogenesis and tumor progression, detected biomarker candidates for early diagnosis, and provided novel therapeutic targets for personalized treatments. Our review focuses on three major topics in EC proteomics: diagnostics, treatment, and molecular mechanisms. We discuss the major histological differences between EC types, i.e., esophageal squamous cell carcinoma and adenocarcinoma, and evaluate the clinical significance of published proteomics studies, including promising diagnostic biomarkers and novel therapeutic targets, which should be further validated prior to launching clinical trials. Multi-disciplinary collaborations between basic scientists, clinicians, and pathologists should be established for inter-institutional validation. In conclusion, EC proteomics has provided significant results, which after thorough validation, should lead to the development of novel clinical tools and improvement of the clinical outcome for esophageal cancer patients. This article is part of a Special Issue entitled: Medical Proteomics.
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Affiliation(s)
- Norihisa Uemura
- Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, chikusa-ku, Nagoya, Aichi 464-8681, Japan.
| | - Tadashi Kondo
- Division of Pharmacoproteomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
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Wang H, Zhang J, Sit WH, Lee CYJ, Wan JMF. Cordyceps cicadae induces G2/M cell cycle arrest in MHCC97H human hepatocellular carcinoma cells: a proteomic study. Chin Med 2014; 9:15. [PMID: 24872842 PMCID: PMC4036300 DOI: 10.1186/1749-8546-9-15] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2013] [Accepted: 04/30/2014] [Indexed: 02/08/2023] Open
Abstract
Background Cordyceps cicadae is a medicinal fungus that is often used for treating cancer. However, the anticancer mechanisms of C. cicadae are largely unknown. This study aims to investigate the anticancer mechanisms of C. cicadae against hepatocellular carcinoma cells in vitro using a proteomic approach. Methods Human hepatocellular carcinoma MHCC97H cells were treated with a water extract of C. cicadae (0, 100, 250, 500, and 1000 μg/mL) for 48 h and harvested for cell viability assays. The significant differences in protein expression between control and C. cicadae-treated cells were analyzed by two-dimensional gel-based proteomics coupled with matrix-assisted laser desorption ionization-time of flight mass spectrometry. Flow cytometry analysis was employed to investigate the cell cycle and cell death. The anticancer molecular mechanism was analyzed by whole proteome mapping. Results The water extract of C. cicadae (0, 100, 250, 500, and 1000 μg/mL) inhibited the growth of MHCC97H cells in a dose-dependent manner via G2/M phase cell cycle arrest with no evidence of apoptosis. Among the identified proteins with upregulated expression were dynactin subunit 2, N-myc downstream-regulated gene 1, heat shock protein beta-1, alpha-enolase isoform 1, phosphatidylinositol transfer protein, and WD repeat-containing protein 1. Meanwhile, the proteins with downregulated expression were 14-3-3 gamma, BUB3, microtubule-associated protein RP/EB family member 1, thioredoxin-like protein, chloride intracellular channel protein 1, ectonucleoside triphosphate diphosphohydrolase 5, xaa-Pro dipeptidase, enoyl-CoA delta isomerase 1, protein-disulfide isomerase-related chaperone Erp29, hnRNP 2H9B, peroxiredoxin 1, WD-40 repeat protein, and serine/threonine kinase receptor-associated protein. Conclusion The water extract of C. cicadae reduced the growth of human hepatocellular carcinoma MHCC97H cells via G2/M cell cycle arrest.
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Affiliation(s)
- Hualin Wang
- Food and Nutrition Division, School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, SAR, China ; School of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, Hubei, China
| | - Jing Zhang
- Food and Nutrition Division, School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, SAR, China
| | - Wai-Hung Sit
- Food and Nutrition Division, School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, SAR, China
| | - Chung-Yung Jetty Lee
- Food and Nutrition Division, School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, SAR, China
| | - Jennifer Man-Fan Wan
- Food and Nutrition Division, School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, SAR, China
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Dvorakova M, Nenutil R, Bouchal P. Transgelins, cytoskeletal proteins implicated in different aspects of cancer development. Expert Rev Proteomics 2014; 11:149-65. [PMID: 24476357 DOI: 10.1586/14789450.2014.860358] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Transgelin is an abundant protein of smooth muscle cells, where its role has been primarily studied. As a protein affecting dynamics of the actin cytoskeleton via stabilization of actin filaments, transgelin is both directly and indirectly involved in many cancer-related processes such as migration, proliferation, differentiation or apoptosis. Transgelin was previously reviewed as a tumor suppressor; however, recent data based on a number of proteomics studies indicate its pro-tumorigenic role, for example, in colorectal or hepatocellular cancer. We summarize these contradictory observations in both clinical and functional proteomics projects and analyze the role of transgelin in tumors in detail. Generally, the expression and biological role of transgelin seem to differ among various types of tumor cells and stroma, and possibly change during tumor progression. We also overview the recent data on transgelin-2, a sequence homolog of transgelin, whose role in the tumor development might be contradictory to the role of transgelin.
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Affiliation(s)
- Monika Dvorakova
- Masaryk Memorial Cancer Institute, Regional Centre for Applied Molecular Oncology, Brno, Czech Republic
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Battle DM, Gunasekara SD, Watson GR, Ahmed EM, Saysell CG, Altaf N, Sanusi AL, Munipalle PC, Scoones D, Walker J, Viswanath Y, Benham AM. Expression of the endoplasmic reticulum oxidoreductase Ero1α in gastro-intestinal cancer reveals a link between homocysteine and oxidative protein folding. Antioxid Redox Signal 2013; 19:24-35. [PMID: 23373818 DOI: 10.1089/ars.2012.4651] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
AIM Ero proteins are central to oxidative protein folding in the endoplasmic reticulum (ER), but their expression varies in a tissue-specific manner. The aim of this work was to establish the expression of Ero1α in the digestive system and to examine the behavior of Ero1α in premalignant Barrett's esophagus, esophageal (OE) and gastric cancers and esophageal cancer cell lines. RESULTS Ero1α is expressed in the columnar epithelium of Barrett's tissue, and in OE tumors and gastric tumors. Homocysteine, a precursor in the metabolism of cysteine and methionine, induces the active Ox1 form of Ero1α in the OE cancer cell line OE33. INNOVATION These results demonstrate for the first time that Ero1α can sense the level of an amino acid precursor, identifying a potential link between diet, antioxidants, and oxidative protein folding in the ER. CONCLUSION The high expression of Ero1α in cancers of the esophagus and stomach demonstrates the importance of ER redox regulation in the gastro-intestinal (GI) tract in health and disease. Proteins and metabolites involved in disulfide bond formation and redox regulation may be suitable targets for both biomarker and drug development in GI cancer.
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Affiliation(s)
- Danielle M Battle
- School of Biological and Biomedical Sciences, Durham University, Durham, England
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Kabbage M, Trimeche M, Ben Nasr H, Hammann P, Kuhn L, Hamrita B, Chahed K. Tropomyosin-4 correlates with higher SBR grades and tubular differentiation in infiltrating ductal breast carcinomas: an immunohistochemical and proteomics-based study. Tumour Biol 2013; 34:3593-602. [PMID: 23812729 DOI: 10.1007/s13277-013-0939-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2013] [Accepted: 06/12/2013] [Indexed: 01/16/2023] Open
Abstract
The aim of this study is to evaluate tropomyosin-4 (TM4) expression in infiltrating ductal breast carcinomas (IDCAs), as well as its prognostic significance. Using a 2-DE/MALDI-TOF mass spectrometry investigation coupled with an immunohistochemical approach, we have assessed the expression of TM4 in IDCAs, as well as in other types of breast tumors. Proteomic analyses revealed an increased expression of tropomyosin-4 in IDCA tumors. Using immunohistochemistry, overexpression of tropomyosin-4 was confirmed in 51 additional tumor specimens. Statistical analyses revealed, however, no significant correlations between tropomyosin-4 expression and clinicopathological parameters of the disease including tumor stage, patient age, estrogen and progesterone receptor status, and lymph node metastasis occurrence. A significant association was found, however, with a high Scarf-Bloom-Richardson (SBR) grade, a known marker of tumor severity. Additionally, the SBR component showing a correlation with TM4 expression was the tubular differentiation status. This study demonstrates the upregulation of tropomyosin-4 in IDCA tissues, which may highlight its involvement in breast cancer development. Our findings also support a link between tropomyosin-4 expression and aggressiveness of IDCA tumors.
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Affiliation(s)
- Maria Kabbage
- Laboratoire d'Immuno-Oncologie Moléculaire, Faculté de Médecine de Monastir, Al Munastir, Tunisia
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Abstract
AIMS Mitochondrial Tu translation elongation factor (TUFM) is a nuclear encoded protein that participates in mitochondrial polypeptide translation. TUFM has been reported to be over-expressed in many tumour types including colorectal carcinoma (CRC) by proteomics. The present study aims to examine the prognostic implication of TUFM in CRC. METHODS Immunohistochemical staining was performed in tissue microarrays composed of 123 cases of CRC using a polyclonal anti-TUFM antibody. Immunoreactivity was quantified using Image-Pro plus software, and analysed in association with patients' clinicopathological parameters and survival time. RESULTS The immunoreactivity of TUFM was negative in 25%, weak in 50% and strong in 25% of CRC cases. TUFM immunoreactivity had no significant association with the clinicopathological parameters examined including TNM stage and grade. However, strong TUFM expression significantly correlated with a higher 5-year recurrence rate (p = 0.024). Kaplan-Meier analysis revealed that patients with strong TUFM expression had significantly shorter cancer-specific survival than patients with negative TUFM (log-rank test, p = 0.038). In multivariate analysis, strong TUFM expression remained a stage-independent unfavourable prognostic indicator (p = 0.024). CONCLUSIONS Increased expression of TUFM is a promising new prognostic indicator for CRC. Selective inhibition of TUFM in tumour cells may present a new avenue for the targeted therapy of this cancer.
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45
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Ceruti P, Principe M, Capello M, Cappello P, Novelli F. Three are better than one: plasminogen receptors as cancer theranostic targets. Exp Hematol Oncol 2013; 2:12. [PMID: 23594883 PMCID: PMC3640925 DOI: 10.1186/2162-3619-2-12] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2013] [Accepted: 03/28/2013] [Indexed: 12/22/2022] Open
Abstract
Activation of plasminogen on the cell surface initiates a cascade of protease activity with important implications for several physiological and pathological events. In particular, components of the plasminogen system participate in tumor growth, invasion and metastasis. Plasminogen receptors are in fact expressed on the cell surface of most tumors, and their expression frequently correlates with cancer diagnosis, survival and prognosis. Notably, they can trigger multiple specific immune responses in cancer patients, highlighting their role as tumor-associated antigens. In this review, three of the most characterized plasminogen receptors involved in tumorigenesis, namely Annexin 2 (ANX2), Cytokeratin 8 (CK8) and alpha-Enolase (ENOA), are analyzed to ascertain an overall view of their role in the most common cancers. This analysis emphasizes the possibility of delineating new personalized therapeutic strategies to counteract tumor growth and metastasis by targeting plasminogen receptors, as well as their potential application as cancer predictors.
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Affiliation(s)
- Patrizia Ceruti
- Center for Experimental Research and Medical Studies (CeRMS), Azienda Ospedaliera Città della Salute e della Scienza, Via Cherasco 15, Turin, 10126, Italy.,Department of Molecular Biotechnology and Health Science, University of Turin, Turin, Italy
| | - Moitza Principe
- Center for Experimental Research and Medical Studies (CeRMS), Azienda Ospedaliera Città della Salute e della Scienza, Via Cherasco 15, Turin, 10126, Italy.,Department of Molecular Biotechnology and Health Science, University of Turin, Turin, Italy
| | - Michela Capello
- Center for Experimental Research and Medical Studies (CeRMS), Azienda Ospedaliera Città della Salute e della Scienza, Via Cherasco 15, Turin, 10126, Italy.,Department of Molecular Biotechnology and Health Science, University of Turin, Turin, Italy
| | - Paola Cappello
- Center for Experimental Research and Medical Studies (CeRMS), Azienda Ospedaliera Città della Salute e della Scienza, Via Cherasco 15, Turin, 10126, Italy.,Department of Molecular Biotechnology and Health Science, University of Turin, Turin, Italy
| | - Francesco Novelli
- Center for Experimental Research and Medical Studies (CeRMS), Azienda Ospedaliera Città della Salute e della Scienza, Via Cherasco 15, Turin, 10126, Italy.,Department of Molecular Biotechnology and Health Science, University of Turin, Turin, Italy
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46
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Zhou L, Zhang R, Zhang L, Sun Y, Yao W, Zhao A, Li J, Yuan Y. Upregulation of transgelin is an independent factor predictive of poor prognosis in patients with advanced pancreatic cancer. Cancer Sci 2013; 104:423-430. [PMID: 23331552 PMCID: PMC7657166 DOI: 10.1111/cas.12107] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2012] [Revised: 12/26/2012] [Accepted: 12/30/2012] [Indexed: 12/31/2022] Open
Abstract
Transgelin is a known actin-binding protein, which plays a role in regulating the functions of smooth muscle cells or fibroblasts. Recent evidence indicates that transgelin is involved in diverse human cancers, yet its role in pancreatic cancer remains unclear. We therefore evaluated the expression characteristics and function of transgelin in pancreatic cancer. Immunohistochemical analysis of benign (n = 30 patients) and malignant (n = 114 patients) pancreatic ductal cells showed significantly higher transgelin staining in malignant cells. Lymph node metastasis (P = 0.026) and diabetes (P = 0.041) were shown to significantly correlate with transgelin protein expression. Patients with high transgelin expression showed a shorter 5-year overall survival and a lower tumor-specific survival than those with low transgelin expression. Multivariate analysis revealed that transgelin was an independent factor affecting pancreatic tumor-specific survival (P = 0.025). In vitro, RNA interference-mediated transgelin knockdown resulted in inhibition of pancreatic cancer cell proliferation, migration and invasion. Depletion of transgelin expression could suppress pancreatic tumorigenicity and tumor growth in vivo, and produce enhanced cytotoxic effects of gemcitabine on pancreatic cancer cells both in vitro and in vivo. Our results indicate that transgelin plays a promoting role in tumor progression, and appears to be a novel prognostic marker for advanced pancreatic cancer.
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Affiliation(s)
- Lin Zhou
- Department of Gastroenterology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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47
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Sugimoto K, Shiraki K, Takei Y, Ito M, Nobori T, Suzuki H, Dissanayaka SK, Meno K, Asashima M, Uchida K. Serum protein isoform profiles indicate the progression of hepatitis C virus-induced liver diseases. Int J Mol Med 2013; 31:943-50. [PMID: 23381678 DOI: 10.3892/ijmm.2013.1267] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2012] [Accepted: 10/15/2012] [Indexed: 11/05/2022] Open
Abstract
Biomarkers that enable an accurate diagnosis of hepatitis C virus (HCV)-induced liver diseases are necessary to prevent subsequent patient morbidity and suffering from the onset of hepatocellular carcinoma (HCC). In particular, the identification of novel biomarkers for liver cirrhosis (LC) will be an important new diagnostic tool since more than 70% of HCV-induced LCs are destined to develop into HCC. In our current study, we performed a search for new serological protein biomarkers of HCV-induced chronic hepatitis (CH), LC and HCC, using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). The disease-affected spots were subsequently identified as isoforms of protein components of haptoglobin, transthyretin, the haptoglobin α-chain and apolipoprotein A-IV (apo A-IV), and in specific instances were significantly reduced in LC (p<0.001) and HCC (p<0.01), compared with CH patients. We further examined these isoforms by receiver operating characteristics (ROC) curve analysis and found that they showed high area under ROC curve (AUC) values of more than 0.8 between CH and LC, suggesting that they are appropriate markers that could be utilized to discriminate LC from CH. In conclusion, protein variants in serum that arise as a result of post-translational modifications prove to be useful biomarkers for the accurate diagnosis of specific liver diseases.
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Affiliation(s)
- Kazushi Sugimoto
- Department of Molecular and Laboratory Medicine, Mie University School of Medicine, Tsu, Japan.
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48
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Liu DP, Qi RZ, Wang Y, Chen PP, Koeffler HP, Xie D. Discovery of stage-related proteins in esophageal squamous cell carcinoma using proteomic analysis. Proteomics Clin Appl 2012; 1:312-20. [PMID: 21136681 DOI: 10.1002/prca.200600815] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Esophageal squamous cell carcinoma (ESCC) is the major subtype of esophageal cancers in China, and characterized with high morbidity and mortality. So far, the diagnosis of ESCC is mainly dependent on the alterations in esophageal histology, but most cases of ESCC with low stage do not display visible histological abnormalities. Therefore, a deep understanding of the mechanism of ESCC progression and seeking stage-specific molecules might improve the diagnosis and therapy for ESCC. In this study, we used proteomics to analyze ESCC tissues with classification by TNM stage, and determined the proteomic features correlated with ESCC progression (from stages I to III). Proteins that exhibited significantly different expression patterns between ESCC and corresponding normal esophageal tissues were identified using MS. The identified proteins with differentiated expression mainly fell into three protein categories (i.e. cytoskeleton system-associated proteins, metabolism enzymes, and heat shock proteins). In addition, real-time PCR highlighted some molecules that were associated with tumor stages at the mRNA level, such as enolase 1, chromosome 1 ORF 10, elastase inhibitor, α B crystalline, stress-induced phosphoprotein 1, and squamous cell carcinoma antigen 1. Altogether, these data provided further information on ESCC progression and potential drug targets for ESCC clinical therapy.
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Affiliation(s)
- Dong-Ping Liu
- Laboratory of Molecular Oncology, Institute for Nutritional Sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China
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Qi YJ, Chao WX, Chiu JF. An overview of esophageal squamous cell carcinoma proteomics. J Proteomics 2012; 75:3129-37. [PMID: 22564818 DOI: 10.1016/j.jprot.2012.04.025] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2012] [Revised: 03/30/2012] [Accepted: 04/18/2012] [Indexed: 12/12/2022]
Abstract
Esophageal squamous cell carcinoma (ESCC) still remains the leading cancer-caused mortality in northern China, in particular in areas nearby Taihang Mountain. Late-stage diagnosis of ESCC increases the mortality and morbidity of ESCC. Therefore, it is imperative to identify biomarkers for early diagnosis, monitoring of tumor progression and identifying potential therapeutic targets of ESCC. Proteomics provides a functional translation of the genome and represents a richer source for the functional description of diseases and biomarkers implicated in cancer. In this review, we discuss the dysregulated proteins associated with ESCC identified by proteomic approaches and aim to enhance our understanding of molecular mechanisms implicated in ESCC development and progression from a proteomics perspective and discuss the potential biomarkers of ESCC as well.
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Affiliation(s)
- Yi-Jun Qi
- Key Laboratory of Cellular and Molecular Immunology, Institute of Immunology, Medical School of Henan University, Kaifeng, Henan, P. R. China
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50
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Differentially Expressed Proteins between Esophageal Squamous Cell Carcinoma and Adjacent Normal Esophageal Tissue. J Med Biochem 2012. [DOI: 10.2478/v10011-011-0048-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Differentially Expressed Proteins between Esophageal Squamous Cell Carcinoma and Adjacent Normal Esophageal Tissue
Proteomics was employed to identify the differentially expressed proteins between esophageal squamous cell carcinoma (ESCC) and adjacent normal esophageal tissues. ESCC tissues and adjacent normal tissues were obtained from 10 patients with ESCC and the proteins were extracted and subjected to two-dimensional gel electrophoresis (2-DE). The differentially expressed proteins were identified after image analysis, and matrix assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF-MS) was used to confirm these proteins. Immunohistochemistry was then performed to detect the expressions of HSP27 and ANX1 in ESCC tissues and adjacent normal tissues. A total of 6 differentially expressed proteins were identified by peptide mass fingerprinting, among which SCCA1, KRT4 and ANX1 were down-regulated and TIM1, MnSOD and HSP27 up-regulated in the ESCC. Immunohistochemistry showed HSP27 was highly expressed in the ESCC which, however, had a low expression of ANX1. These findings were consistent with those in proteomics. There were differentially expressed proteins between ESCC and adjacent normal tissues. The investigation of differentially expressed proteins between ESCC and normal esophageal tissue may provide evidence for the molecular pathogenesis of ESCC.
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