|
1
|
Mohammedsaleh ZM, Moawadh MS, Saleh FM, Jalal MM, Al-Otaibi AS, Saeedi NH, Baskaran R, Huang CY, Kumar VB. Increased NOTCH1 expression is associated with low survival in moderate/ poor differentiated human oral squamous cell carcinoma patients. J Cancer 2023; 14:3023-3027. [PMID: 37859809 PMCID: PMC10583578 DOI: 10.7150/jca.87128] [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: 06/14/2023] [Accepted: 09/09/2023] [Indexed: 10/21/2023] Open
Abstract
Notch deregulation has been reported in various types of cancers, including Oral squamous cell carcinomas (OSCCs). The role of Notch1 signaling in oral squamous cell carcinoma (OSCC) remains poorly understood. In this study, NOTCH1 was aberrantly expressed in human oral cancer tissues compared with that in normal marginal tissues and was associated with poor prognosis. The positive Notch 1 expression was significantly associated with poor tumor differentiation status. Kaplan-Meier survival curves revealed that elevated cytoplasmic NOTCH1 expression levels in OSCC patients were associated with poor overall survival. Moreover, multivariate COX proportional hazard models revealed that T N status, AJCC stage histological grade were independent prognostic factors for survival. Our result clearly demonstrates the oncogenic role of Notch1 in oral cancer and Notch1 may be a useful biomarker to target oral cancer patients.
Collapse
Affiliation(s)
- Zuhair M. Mohammedsaleh
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Mamdoh S. Moawadh
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Fayez M. Saleh
- Department of Medical Microbiology, Faculty of Medicine, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Mohammed M. Jalal
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Abdulaziz S Al-Otaibi
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Nizar H. Saeedi
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Rathinasamy Baskaran
- Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan
| | - Chih-Yang Huang
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan
| | - V. Bharath Kumar
- Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung 413, Taiwan
| |
Collapse
|
|
2
|
A homogalacturonan from Lonicera japonica Thunb. disrupts angiogenesis via epidermal growth factor receptor and Delta-like 4 associated signaling. Glycoconj J 2022; 39:725-735. [PMID: 36306024 DOI: 10.1007/s10719-022-10088-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 09/01/2022] [Accepted: 10/11/2022] [Indexed: 01/09/2023]
Abstract
A homogeneous polysaccharide named as LJW2F2 was extracted and purified from the flowers of Lonicera japonica Thunb. Structural characteristic indicated that LJW2F2 was a homogalacturonan composed of α-1,4-D-galacturonic acid with a molecular weight of 7.2 kDa. Previous investigation suggested that homogalacturonan might impede angiogenesis, however the mechanism is still vague. Here we reported that LJW2F2 significantly disrupted capillary-like tube formation of human microvascular endothelia cells (HMEC-1) on matrigel as well as the cells migration. Mechanism study revealed that LJW2F2 might inactivate phosphorylation of epidermal growth factor receptor (EGFR), subsequently suppress Raf, mitogen-activated protein kinase (MEK) and extracellular-related kinase (ERK) phosphorylation. Moreover, LJW2F2 markedly decreased the expression of Notch1 and Delta-like ligand 4 (Dll4). Therefore, our results suggested that LJW2F2 might be a potential angiogenesis inhibitor via disturbing multiple signaling pathways.
Collapse
|
|
3
|
Ge L, Liu SF. Lentivirus-Mediated Short Hairpin RNA for Follistatin Downregulation Suppresses Tumor Progression in Hypopharyngeal Carcinoma. Curr Med Sci 2022; 42:832-840. [DOI: 10.1007/s11596-022-2615-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 12/21/2021] [Indexed: 11/24/2022]
|
|
4
|
NOTCH1 Intracellular Domain and the Tumor Microenvironment as Prognostic Markers in HNSCC. Cancers (Basel) 2022; 14:cancers14041080. [PMID: 35205828 PMCID: PMC8870336 DOI: 10.3390/cancers14041080] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 02/04/2022] [Accepted: 02/10/2022] [Indexed: 02/05/2023] Open
Abstract
Simple Summary In the head and neck, a large proportion of squamous cell carcinoma demonstrate a mutation of the NOTCH1 gene. The aim of this project was to investigate the role of NOTCH1 and immunological characteristics and highlight a potential rationale for therapy. We found that a high expression of NOTCH1 intracellular domain in these patients is associated with reduced overall survival. In vitro experiments additionally showed a reduction of migration and proliferation of cancer cells when NOTCH1 was knocked down. NOTCH1 is, therefore, most likely involved in migration and proliferation of head and neck squamous cell carcinoma and is a prognostic marker in these patients. Abstract (1) Background: NOTCH1 is the second most common mutated gene in whole-exome sequencing of HNSCC. The aim of this project was to gain further insight into the relevance of NOTCH1 in HNSCC, potentially establishing NOTCH1 as a prognostic marker or therapeutic target; (2) Methods: NOTCH1 was silenced via RNA interference in six HNSCC cell lines and the impact was evaluated in migration and proliferation assays. Subsequently, the protein expression of NOTCH1 intracellular domain (NICD) and NOTCH1 mRNA expression were examined in 70 oropharyngeal squamous cell cancer tissue samples. Lastly, the NICD expression was compared with the local infiltration of lymphocytes, measured with the immunoscore; (3) Results: Knockdown of NOTCH1 decreased migration and proliferation. A high NICD expression was associated with lower OS. A high immunoscore resulted in significantly better OS. NICD expression was independent of the immunoscore and as a whole differentiated three distinct prognostic groups; (4) Conclusions: These data suggest that NOTCH1 is involved in migration and proliferation of HNSCC cell lines. In vivo, NICD expression was associated with overall survival and could, therefore, be used as a prognostic marker. NICD expression differs from NOTCH1 mRNA levels, potentially explaining the previously suggested bimodal role as an oncogene and tumor suppressor in HNSCC.
Collapse
|
|
5
|
Liu C, Xuan LQ, Li K, Feng Z, Lv C, Li XJ, Ji XD, Wan R, Shen J. Shikonin Inhibits Cholangiocarcinoma Cell Line QBC939 by Regulating Apoptosis, Proliferation, and Invasion. Cell Transplant 2021; 30:963689720979162. [PMID: 33508949 PMCID: PMC7863558 DOI: 10.1177/0963689720979162] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
This study was designed to clarify whether Shikonin causes proliferation, apoptosis, and invasion in cholangiocarcinoma cells and to investigate the mechanism of action. QBC939 cells were cultured with different doses of Shikonin, and then 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium assay was used to detect cell viability. Apoptosis of cells was detected using flow cytometry with Annexin V/propidium iodide (PI) assay after being stained with Hoechst 33242. The role of Shikonin on the invasive and metastasis ability was detected using Transwell invasion assay. Real-time polymerase chain reaction and Western blotting were used to detect the expression of caspase-3, caspase-8, epidermal growth factor receptor (EGFR), and matrix metalloproteinase (MMP)-9. Shikonin inhibited proliferation and invasive ability of QBC939 cells in a dose-dependent manner; at the same time, apoptosis of cells was also observed in a concentration-dependent fashion. Moreover, Annexin V/PI assay and Transwell invasion assay results indicated that Shikonin induced apoptosis and invasion inhibitory probably due to upregulation of caspase-3 and caspase-8 expression and downregulation of MMP-9 and EGFR expression in a concentration-dependent fashion. Shikonin could enhance apoptosis and inhibit proliferation and invasion of QBC939 cells; such biological behaviors mainly occurred via upregulating the expression of caspase-3 and caspase-8 and downregulating the expression of MMP-9 and EGFR.
Collapse
Affiliation(s)
- Chang Liu
- Department of Gastroenterology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China
| | - Li-Qian Xuan
- Department of Digestive Endoscopy Center, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China
| | - Kai Li
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
| | - Zhuo Feng
- Department of Digestive Endoscopy Center, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China
| | - Chan Lv
- Department of Gastroenterology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China
| | - Xing-Jia Li
- Department of Gastroenterology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China
| | - Xiao-Dan Ji
- Department of Gastroenterology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China
| | - Rong Wan
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
| | - Jie Shen
- Department of Digestive Endoscopy Center, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, P. R. China.,Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
| |
Collapse
|
|
6
|
Shah PA, Huang C, Li Q, Kazi SA, Byers LA, Wang J, Johnson FM, Frederick MJ. NOTCH1 Signaling in Head and Neck Squamous Cell Carcinoma. Cells 2020; 9:cells9122677. [PMID: 33322834 PMCID: PMC7764697 DOI: 10.3390/cells9122677] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 12/04/2020] [Accepted: 12/08/2020] [Indexed: 12/12/2022] Open
Abstract
Biomarker-driven targeted therapies are lacking for head and neck squamous cell carcinoma (HNSCC), which is common and lethal. Efforts to develop such therapies are hindered by a genomic landscape dominated by the loss of tumor suppressor function, including NOTCH1 that is frequently mutated in HNSCC. Clearer understanding of NOTCH1 signaling in HNSCCs is crucial to clinically targeting this pathway. Structural characterization of NOTCH1 mutations in HNSCC demonstrates that most are predicted to cause loss of function, in agreement with NOTCH1's role as a tumor suppressor in this cancer. Experimental manipulation of NOTCH1 signaling in HNSCC cell lines harboring either mutant or wild-type NOTCH1 further supports a tumor suppressor function. Additionally, the loss of NOTCH1 signaling can drive HNSCC tumorigenesis and clinical aggressiveness. Our recent data suggest that NOTCH1 controls genes involved in early differentiation that could have different phenotypic consequences depending on the cancer's genetic background, including acquisition of pseudo-stem cell-like properties. The presence of NOTCH1 mutations may predict response to treatment with an immune checkpoint or phosphatidylinositol 3-kinase inhibitors. The latter is being tested in a clinical trial, and if validated, it may lead to the development of the first biomarker-driven targeted therapy for HNSCC.
Collapse
Affiliation(s)
- Pooja A. Shah
- Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (P.A.S.); (L.A.B.)
| | - Chenfei Huang
- Bobby R. Alford Department of Otolaryngology, Baylor College of Medicine, Houston, TX 77030, USA; (C.H.); (M.J.F.)
| | - Qiuli Li
- Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China;
| | - Sawad A. Kazi
- School of Natural Sciences, University of Texas, Austin, TX 78712, USA;
| | - Lauren A. Byers
- Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (P.A.S.); (L.A.B.)
- The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA;
| | - Jing Wang
- The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA;
- Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Faye M. Johnson
- Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; (P.A.S.); (L.A.B.)
- The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA;
- Correspondence: ; Tel.: +1-713–792-6363; Fax: +1-713-792-1220
| | - Mitchell J. Frederick
- Bobby R. Alford Department of Otolaryngology, Baylor College of Medicine, Houston, TX 77030, USA; (C.H.); (M.J.F.)
| |
Collapse
|
|
7
|
Jing P, Zhou S, Xu P, Cui P, Liu X, Liu X, Liu X, Wang H, Xu W. PDK1 promotes metastasis by inducing epithelial–mesenchymal transition in hypopharyngeal carcinoma via the Notch1 signaling pathway. Exp Cell Res 2020; 386:111746. [DOI: 10.1016/j.yexcr.2019.111746] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Revised: 11/20/2019] [Accepted: 11/23/2019] [Indexed: 12/19/2022]
|