The purpose of this study was to investigate how miR-200b-3p inhibits the proliferation and metastasis of endometrial cancer cells by inducing the expression of FOSL2 in the AP1 transcription family. Endometrial cancer cell line HEC-1-A was divided into 16 groups: NC-mimic (transfected with negative control NC mimic), miR-200b-3p mimic (transfected with miR-200b-3p mimic), NC-suppress (transfected with negative control NC inhibit), miR-200b-3p inhibit group (transfected with miR-200b-3p inhibit), si-NC (transfected with negative control si-NC), si-FOSL2 (transfected with Si-FOSL2), oe-NC (transfected with negative control oe-NC), oe-FOSL2 group (oe-FOSL2), miR-200b-3p mimic + oe-NC group (co-transfected with miR-200b-3p mimic and oe-NC), miR-200b-3p mimic + oe-FOSL2 group (co-transfected with miR-200b-3p mimic and oe-FOSL2), miR-200b-3p inhibit + si-NC group (co-transfected with miR-200b-3p inhibit and si-NC), miR-200b-3p inhibit + si-FOSL2 group (co-transfected with miR-200b-3p inhibit and si-FOSL2), miR-200b-3p mimic + si-NC group (co-transfected with miR-200b-3p mimic and si-NC), miR-200b-3p mimic + si-FOSL2 group (co-transfected with miR-200b-3p mimic and si-FOSL2), miR-200b-3p inhibit + oe-NC group (co-transfected with miR-200b-3p inhibit and oe-NC), miR-200b-3p inhibit + oe-FOSL2 group (co-transfected with miR-200b-3p inhibit and oe-FOSL2). Real-time fluorescence quantitative PCR, Western blot, CCK-8 assay, scratch test and Transwell assay were used to detect the expression of miR-200b-3p mRNA, FOSL2 mRNA and protein, cell proliferation, migration and invasion. In endometrial cancer cell lines, the expression of miR-200b-3p was significantly down-regulated (P < 0.05), while the expression of FOSL2 was significantly up-regulated (P < 0.05). Compared with NC-mimic group, the expression of FOSL2, N-cadherin and Vimentin in miR-200b-3p mimic group was significantly decreased (P < 0.05), and the expression of E-cadherin was significantly increased (P < 0.05). The cell proliferation, migration rate and the number of transmembrane cells were significantly decreased (P < 0.05). Compared with the miR-200b-3p mimic + oe-NC group, the expression of FOSL2, N-cadherin and Vimentin in miR-200b-3p mimic + oe-FOSL2 was significantly increased (P < 0.05), the expression level of E-cadherin was significantly decreased (P < 0.05), and the cell proliferation, migration rate and the number of transmembrane cells were significantly increased (P < 0.05). Compared with NC-inhibit group, the expression of FOSL2, N-cadherin and Vimentin in miR-200b-3p inhibit group was significantly increased (P < 0.05), and the expression of E-cadherin was significantly decreased (P < 0.05). The cell proliferation, migration rate and the number of transmembrane cells were significantly increased (P < 0.05). Compared with the miR-200b-3p inhibit + si-NC group, the expression of FOSL2, N-cadherin and Vimentin in miR-200b-3p inhibit + si-FOSL2 was significantly decreased (P < 0.05), and the expression of E-cadherin was significantly increased (P < 0.05); the cell proliferation, migration rate and the number of transmembrane cells were significantly decreased (P < 0.05) The expression of miR-200b-3p in endometrial cancer cells is down-regulated, which can inhibit the proliferation, migration and invasion of endometrial cancer cells by regulating the EMT process, and its mechanism is related to its targeted negative regulation of FOSL2 expression.

The process of epithelial-mesenchymal transition (EMT) is crucial in various physiological/pathological circumstances such as development, wound healing, stem cell behavior, and cancer progression. It involves the conversion of epithelial cells into a mesenchymal phenotype, which causes the cells to become highly motile. This reprogramming is initiated and controlled by various signaling pathways and governed by several key transcription factors, including Snail 1, Snail 2 (Slug), TWIST 1, TWIST2, ZEB1, ZEB2, PRRX1, GOOSECOID, E47, FOXC2, SOX4, SOX9, HAND1, and HAND2. The intracellular signaling pathways are activated/inactivated by signals received from the extracellular environment and the transcription factors are carefully regulated at the transcriptional, translational, and post-translational levels to maintain tight regulatory control of EMT. One of the most important pathways involved in this process is the transforming growth factor-β (TGFβ) family signaling pathway. This review will discuss the role of EMT in promoting epithelial cancer progression and the convergence/interplay of multiple signaling pathways and transcription factors that regulate this phenomenon.

To evaluate the efficiency of 68Ga-FAPI-04 PET (PET/MRI or PET/CT) for N and M staging in gastric carcinoma and compare outcomes with histopathology and contrast-enhanced computed tomography (CECT).

Patients with gastric carcinoma who had undergone 68Ga-FAPI-04 PET/MRI or PET/CT before treatment were retrospectively enrolled. Histopathology post lymphadenectomy was the gold standard for N staging, while histopathology and follow-up data were the reference for overall outcomes. The diagnostic efficiency of 68Ga-FAPI-04 PET for detecting regional lymph node involvement and distant metastases was compared to that of CECT.

Sixty-two patients were enrolled. In 18 patients who underwent 68Ga-FAPI-04 PET/MRI and lymphadenectomy, 532 lymph nodes were dissected. 68Ga-FAPI-04 PET/MRI showed similar sensitivity, specificity, and accuracy compared to CECT (28.3% vs. 23.2%, 99.8% vs. 99.3%, and 86.5% vs. 85.2%, all P > 0.05). Fifty-five patients had regional lymph node metastasis, 68Ga-FAPI-04 PET exhibited comparable diagnostic efficiency to CECT, with sensitivity of 83.6% versus 87.3%, specificity of 100% versus 85.7%, accuracy of 85.5% versus 87.1% (all P > 0.05). Excluding 3 patients with only abdominal CECT, 32 out of 59 patients had distant metastasis, with no significant differences in sensitivity, specificity, and accuracy between 68Ga-FAPI-04 PET and CECT based on patient (100% vs. 87.5%, 92.6% vs. 96.3%, and 96.6% vs. 91.5%, all P >0.05). Notably, 68Ga-FAPI-04 PET outperformed CECT in detecting peritoneal, distant lymph nodes, bone, liver, and ovarian metastases by visualizing more lesions or greater lesion extent.

68Ga-FAPI-04 PET exhibits comparable diagnostic performance to CECT for patient-based N staging and M staging of gastric cancer. However, it surpasses CECT in visualizing distant metastases.

Several types of cancer, including breast cancer, metastasize to the lung. However, before the disseminating tumor cells (DTCs) arrive there, the lung must be prepared as a hospitable environment for them, forming the pre-metastatic niche (PMN). It is now accepted that the primary tumor can release soluble mediators or extracellular vesicles that activate the PMN resident cells, recruit immune cells, promote angiogenesis, and remodel the extracellular matrix (ECM), even before the arrival of DTCs to the niche. However, not all the components of the tumor secretome are known. Here we demonstrate in a mouse model of breast cancer designed to generate lung PMN, that EMMPRIN, a multifunction protein and mediator of tumor-stroma cell interactions, is part of that secretome. To study the involvement of EMMPRIN in the generation of lung PMN, we knocked down its expression in D2A1 cells (D2A1-KD), treated the mice with the anti-EMMPRIN antibody developed in our lab (m161-pAb), or administered the recombinant EMMPRIN protein to healthy mice. We show that the primary tumor released elevated levels of EMMPRIN in mice implanted with paternal D2A1 cells (D2A1-WT), generating lung PMN by increasing VEGF, MMP-9 and TGFβ secretion, enhancing angiogenesis, activating fibroblasts, increasing neutrophils infiltration, and remodeling the ECM. These effects were inhibited in mice implanted with D2A1-KD cells or administered with m161-pAb. In healthy mice, the recombinant EMMRPIN recapitulated the effects of high EMMPRIN levels. Thus, EMMPRIN as part of the tumor secretome is sufficient to promote the lung PMN, and targeting it could potentially inhibit the metastatic cascade.

Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors in the world, and its incidence and mortality have increased year by year. HCC research has increasingly focused on understanding its pathogenesis and developing treatments.The Wnt signaling pathway, a complex and evolutionarily conserved signal transduction system, has been extensively studied in the genesis and treatment of several malignant tumors. Recent investigations suggest that the pathogenesis of HCC may be significantly influenced by dysregulated Wnt/β-catenin signaling. This article aimed to examine the pathway that controls Wnt signaling in HCC and its mechanisms. In addition, we highlighted the role of this pathway in HCC etiology and targeted treatment.

T cell engagers (TCEs) represent a groundbreaking advancement in the treatment of B and plasma cell malignancies and are emerging as a promising therapeutic approach for the treatment of solid tumors. These molecules harness T cells to bind to and eliminate cancer cells, effectively bypassing the need for antigen-specific T cell recognition. Despite their established clinical efficacy, a subset of patients is either refractory to TCE treatment (e.g. primary resistance) or develops resistance during the course of TCE therapy (e.g. acquired or treatment-induced resistance). In this review we comprehensively describe the resistance mechanisms to TCEs, occurring in both preclinical models and clinical trials with a particular emphasis on cellular and molecular pathways underlying the resistance process. We classify these mechanisms into tumor intrinsic and tumor extrinsic ones. Tumor intrinsic mechanisms encompass changes within tumor cells that impact the T cell-mediated cytotoxicity, including tumor antigen loss, the expression of immune checkpoint inhibitory ligands and intracellular pathways that render tumor cells resistant to killing. Tumor extrinsic mechanisms involve factors external to tumor cells, including the presence of an immunosuppressive tumor microenvironment (TME) and reduced T cell functionality. We further propose actionable strategies to overcome resistance offering potential avenues for enhancing TCE efficacy in the clinic.

Cellular senescence is one of the key steps in the progression of pulmonary fibrosis, and the senescence of type II alveolar epithelial cells (AEC IIs) may potentially accelerate the progression of pulmonary fibrosis. However, the molecular mechanisms underlying cellular senescence in pulmonary fibrosis remain unclear.

The researchers first conducted in vitro experiments to investigate whether AEC IIs cultured on high matrix stiffness would lead to cellular senescence. Next, samples from mouse pulmonary fibrosis models and clinical idiopathic pulmonary fibrosis (IPF) patients were tested to observe extracellular matrix deposition, lamin A/C levels, and cellular senescence status in lung tissue. Construct lamin A/C knockdown and overexpression systems separately in AEC IIs, and observe whether changes in lamin A/C levels lead to cellular senescence. Further explore the degradation mechanism of lamin A/C using protein degradation inhibitors.

In vitro experiments have found that high matrix stiffness promotes senescence of AEC IIs. In a mouse model of pulmonary fibrosis, AEC IIs were found to exhibit significant cellular senescence on day 21. In clinical IPF samples, it was found that senescent cells expressed low levels of lamin A/C. In the lamin A/C SiRNA knockdown system, it was further confirmed that AEC IIs with low levels of lamin A/C are more prone to cellular senescence. Under high matrix stiffness, lamin A/C in AEC IIs is degraded through the autophagy lysosome pathway. The use of chloroquine can effectively alleviate cellular senescence.

High matrix stiffness degrades lamin A/C in pulmonary fibrosis through lysosomal degradation pathways, promoting AEC II senescence. Inhibition the degradation of lamin A/C could alleviate AEC II senescence.

Research the expression of USP4 in lung adenocarcinoma and its correlation with clinicopathological features and prognosis analysis, to explore the invasion and metastasis mechanism of USP4 in lung adenocarcinoma, and to clarify the mechanism of USP4's involvement in the occurrence and development of lung adenocarcinoma. The expressions of USP4, VEGF, MMP2 and Ki67 in lung adenocarcinoma and adjacent tissues of 139 patients with lung adenocarcinoma were detected by immunohistochemical method, and the correlation between expression and clinicopathological features and survival curve were analyzed by statistical method. The expression of USP4 was interfered by LIP-2000 cell transfection technology, and the expression of USP4 and its related factors in protein level was detected by Western Blot, and their correlation was analyzed. After silencing USP4 expression, the effects of USP4 on proliferation, invasion and migration of lung adenocarcinoma cells were detected by cell scratches assay, MTT assay, Transwell assay and tumorigenesis assay in nude mice. The expression of USP4 in lung adenocarcinoma tissues was higher than that in normal adjacent tissues, and the high expression of USP4 was significantly correlated with the differentiation degree of lung adenocarcinoma, clinical stage and pathological grade lymph node metastasis. After silencing USP4 expression, the expression of cyclin apoptosis protein invasion related proteins and phosphorylation factors were affected, and then cell migration and the proliferation ability decreased, the number of invasion and metastasis decreased, and the tumor volume decreased in nude mice. USP4 may play a certain role in the invasion and metastasis of lung adenocarcinoma by regulating the expression of tumor-related factors and affecting the prognosis of patients with lung adenocarcinoma. USP4 can be used as a potential therapeutic target for clinical diagnosis of lung adenocarcinoma and provide a new opportunity for clinical research on lung adenocarcinoma.

Although various treatment options are available for prostate cancer (PCa), including androgen deprivation therapy (ADT) and chemotherapy, these approaches have not achieved the desired results clinically, especially in the treatment of advanced chemotherapy-resistant PCa. The PI3K/AKT/mTOR (PAM) signaling pathway is a classical pathway that is aberrantly activated in cancer cells and promotes the tumorigenesis, metastasis, resistance to castration therapy, chemoresistance, and recurrence of PCa. Noncoding RNAs (ncRNAs) are a class of RNAs that do not encode proteins. However, some ncRNAs have recently been shown to be differentially expressed in tumor tissues compared with noncancerous tissues and play important roles at the transcription and posttranscription levels. Among the types of ncRNAs, long noncoding RNAs (lncRNAs), microRNAs (miRNAs), circular RNAs (circRNAs), and Piwi-interacting RNAs (piRNAs) can participate in the PAM pathway to regulate PCa growth, metastasis, angiogenesis, and tumor stemness. Therefore, ncRNA therapy that targets the PAM signaling pathway is expected to be a novel and effective approach for treating PCa. In this paper, we summarize the types of ncRNAs that are associated with the PAM pathway in PCa cells as well as the functions and clinical roles of these ncRNAs in PCa. We hope to provide novel and effective strategies for the clinical diagnosis and treatment of PCa.

Autism spectrum disorder (ASD) is a set of heterogeneous neurodevelopmental conditions, the etiology of which remains elusive. Sialic acid (SA) is an essential nutrient for nervous system development, and previous studies reported that the levels of SA were decreased in the blood and saliva of ASD children. However, it is not clear whether SA supplementation can alleviate behavioral problems in autism. We administered SA intervention in the VPA-induced autism model rats, evaluated behavior performance, and measured the levels of Gne and St8sia2 genes, BDNF and anti-GM1. At the same time, untargeted metabolomics was used to characterize the metabolites. It was found that the stereotypical behaviors, social preference and cognitive function were improved after SA supplementation. Additionally, the number of hippocampal neurons was increased, and the shape was normalized. Moreover, 94 differentially abundant metabolites were identified between the high dose SA and VPA groups. These changes in metabolites were correlated with pyrimidine metabolism, lysine degradation metabolism, biosynthesis of amino acids, mineral absorption, protein digestion and absorption, galactose metabolism, phenylalanine, tyrosine and tryptophan biosynthesis and phenylalanine metabolism. In conclusion, SA could ameliorate ASD-like phenotypes and change metabolites in autistic animals, which suggests that it may be a therapeutic approach for ASD.

CXCL8, belonging to inflammatory chemokines, is expressed by various cell types and plays a key role in leukocyte trafficking during infections, inflammatory processes, tissue injury and tumor progression. Chemokines interact not only with G-protein coupled receptors but also with glycosaminoglycans (GAGs), which are polyanionic linear polysaccharides. Chemokine-GAG interactions are critical for creating localized concentration gradients, protecting chemokines from degradation, and maintaining their efficacy in vivo.

We have previously engineered a CXCL8-based dominant-negative decoy ("PA401") with strongly increased GAG binding affinity combined with complete GPCR knockout, which was originally developed for the treatment of COPD. Here we have optimized our engineering protocol by minimizing CXCL8 mutations while conserving its in vitro dominant-negative activities. This novel CXCL8-based decoy (mtCXCL8) was further fused to human serum albumin (HSA) to overcome the typically very short serum half-life of chemokine-based biologics. We are therefore able to present here an entirely novel CXCL8-based biologic (hsa/mtCXCL8) which reflects our threefold modification strategy - increasing GAG-binding affinity by minimal mutagenesis, GPCR knockout, and fusion to HSA - thus representing a comprehensive and novel approach towards addressing chronic CXCL8-driven diseases.

In the current study, we have investigated the immunomodulatory potential of our new decoy in a 3-D cellular tumor model ("BioMAP") which relates the biomarker interaction profile of immune and tumor cells to a data-base mirrored biomarker read-out. The obtained BioMAP results suggest an impact of hsa/mtCXCL8 on the immune compartment of the VascHT29 cell model by modulating cytokine levels and inhibiting immune cell activation markers. When combined with Keytruda (Pembrolizumab), a PD-1 inhibitor, it enhances some of its known activities, indicating potential synergistic effects, but further investigation is needed due to the observed increase in soluble IL-6 and limitations in dose selection for future in vivo studies.

By prolonging the presence of engineered chemokine mutants in the bloodstream and optimizing their stability, these strategies aim to enhance the therapeutic efficacy of CXCL8-based interventions, offering promising avenues for the treatment of several CXCL8-mediated pathologies, including cancer.

Targeted therapy is an effective strategy for the treatment of advanced and metastatic pancreatic cancer, one of the leading causes for cancer-related death worldwide. To address the limitations of existing targeted drugs, there is an urgently need to find novel targets and therapeutic strategies. Transcription factor FOS like 1 (FOSL1) is a potential therapeutic target for challenging pancreatic cancer, which contributes to the malignant progression and poor gnosis of pancreatic cancer. High mobility group A1 (HMGA1) is a nonhistone chromatin structural protein that contributes to malignant progression and poor prognosis of cancer.

Human FOSL1 complete RNA, shRNA against FOSL1 and shRNA against HMGA1 lentiviral recombination vectors were used to overexpress FOSL1 and knock down FOSL1 and HMGA1. RNA sequencing, Q-PCR and Western blots were used to investigate the mechanism of FOSL1 in regulating the proliferation of pancreatic cancer cells. The relationship between FOSL1 and HMGA1 were analyzed by co-immunoprecipitation Mass spectrometry, Q-PCR of chromatin immunoprecipitation and Western blots. The regulation of FOSL1 and HMGA1 in the invasion and migration, stemness, and multidrug efflux system were determined by transwell assay, sphere formation assay, immunofluorescence, Q-PCR and Western blots.

We found that FOSL1 promoted the proliferation and progression of pancreatic cancer by trigging stemness, invasion and metastasis, and drug resistance. HMGA1 was a key downstream target regulated by FOSL1 at the transcriptional level and directly interacted with FOSL1. Knockdown of HMGA1 inhibited the proliferation of pancreatic cancer cells by regulating the expression of genes related to stemness, epithelial-mesenchymal transition and multidrug efflux system. Targeted inhibition of FOSL1 and HMGA1 expression significantly inhibited the proliferation of pancreatic cancer cells.

FOSL1 promote the malignant progression of pancreatic cancer by promoting HMGA1 expression. Targeting FOSL1 and HMGA1 in monotherapy or combination therapy is a promising strategy for the treatment of advanced and metastasis pancreatic cancer.

Ovarian cancer (OC) is one of the most prevalent gynecologic malignancies and exhibites the highest fatality rate among all gynecologic malignancies. The absence of an early diagnostic biomarker and therapeutic target contributes to an overall 5-year survival rate ranging from 30 to 50%. Plectin (PLEC), a 500 kDa scaffolding protein, has gained prominence in recent years due to its pivotal role in various cellular biological functions such as cell morphology, migration and adhesion, while the accurate role of PLEC in OC remains elusive.

In this study, our findings demonstrate that PLEC exerts a positive influence on the progression of OC, encompassing cellular proliferation, migration, invasion, and adhesion both in vitro and in vivo.

The results providing new insights for the diagnosis and treatment in OC.

The lung is a highly vascularized tissue that often harbors metastases from various extrathoracic malignancies. Lung parenchyma consists of a complex network of alveolar epithelial cells and microvessels, structured within an architecture defined by basement membranes. Consequently, understanding the role of the extracellular matrix (ECM) in the growth of lung metastases is essential to uncover the biology of this pathology and developing targeted therapies. These basement membranes play a critical role in the progression of lung metastases, influencing multiple stages of the metastatic cascade, from the acquisition of an aggressive phenotype to intravasation, extravasation and colonization of secondary sites. This review examines the biological composition of basement membranes, focusing on their core components-collagens, fibronectin, and laminin-and their specific roles in cancer progression. Additionally, we discuss the function of integrins as primary mediators of cell adhesion and signaling between tumor cells, basement membranes and the extracellular matrix, as well as their implications for metastatic growth in the lung. We also explore vascular co-option (VCO) as a form of tumor growth resistance linked to basement membranes and tumor vasculature. Finally, the review covers current clinical therapies targeting tumor adhesion, extracellular matrix remodeling, and vascular development, aiming to improve the precision and effectiveness of treatments against lung metastases.

Metastasis is currently becoming a major clinical concern, due to its potential to cause therapeutic resistance. Its development involves a series of phases that describe the metastatic cascade: preparation of the pre-metastatic niche, epithelial-mesenchymal transition, dissemination, latency and colonization of the new tissue. In the last few years, new therapeutic targets, such as integrins, are arising to face this disease. Integrins are transmembrane proteins found in every cell that have a key role in the metastatic cascade. They intervene in adhesion and intracellular signaling dependent on the extracellular matrix and cytokines found in the microenvironment. In this case, integrins can initiate the epithelial-mesenchymal transition, guide the formation of the pre-metastatic niche and increase tumor migration and survival. Integrins also take part in the tumor vascularization process necessary to sustain metastasis. This fact emphasizes the importance of inhibitory therapies capable of interfering with the function of integrins in metastasis.

The dysregulation of matrix metalloproteinases (MMPs) in skin cutaneous melanoma (SKCM) represents a critical aspect of tumorigenesis. In this study, we investigated the diagnostic, prognostic, and therapeutic aspects of the MMPs in SKCM. Thirteen SKCM cell lines and seven normal skin cell lines were cultured under standard conditions for experimental analyses. RNA and DNA were extracted, followed by RT-qPCR to assess MMP expression and promoter methylation analysis to determine methylation levels. Functional assays, including cell proliferation, colony formation, and wound healing, were conducted post-MMP7 knockdown using siRNA in A375 cells. Databases like GEPIA2, HPA, MEXPRESS, and miRNet were employed for expression, survival, methylation, and miRNA-mRNA network analyses. We investigated the expression and promoter methylation landscape of MMPs in SKCM cell lines, revealing significant (p-value < 0.05) up-regulation of MMP1, MMP7, MMP9, MMP10, MMP11, MMP12, MMP13, MMP14, and MMP25, alongside down-regulation of MMP2, MMP3, and MMP21. Furthermore, our analysis demonstrated a significant (p-value < 0.05) inverse correlation between MMP expression levels and promoter methylation status, suggesting a potential regulatory role of DNA methylation in MMP dysregulation. Notably, MMP7, MMP11, and MMP14 exhibited significant (p-value < 0.05) associations with the overall survival of SKCM patients, emphasizing their prognostic significance. Additionally, Receiver operating characteristic (ROC) curve analysis highlighted the significant (p-value < 0.05) diagnostic potential of MMP7, MMP11, and MMP14 in distinguishing SKCM from normal individuals. Subsequent validation across multiple cohorts confirmed significant (p-value < 0.05) elevated MMP expression levels in SKCM tissues, particularly in advanced disease stages, further emphasizing their role in tumor progression. Furthermore, we elucidated potential regulatory pathways involving miR-22-3p, which targets MMP7, MMP11, and MMP14 genes in SKCM. Our findings also revealed associations between MMP expression and immune modulation, drug sensitivity, and functional states of SKCM cells. Lastly, MMP7 knockdown in A375 cells significantly significant (p-value < 0.05) impacted several characteristics, including cell proliferation, colony formation, and wound healing. Our findings highlight the diagnostic, prognostic, and therapeutic potential of MMP7, MMP11, and MMP14 in SKCM. These MMPs could serve as biomarkers for early detection and targets for therapy. Future efforts should focus on preclinical and clinical validation to translate these insights into personalized diagnostic and therapeutic strategies.

This study provides an in-depth analysis of the pathogenic relevance, therapeutic implications, and mechanisms of treatment resistance associated with TLR4 and its ncRNAs in cancer immunopathogenesis. TLR4, a pivotal component of the innate immune response, has been implicated in promoting inflammation, tumorigenesis, and immune evasion across various malignancies, including gastric, ovarian, and hepatocellular carcinoma. The interactions between TLR4 and specific ncRNAs, such as lncRNAs and miRNAs, play a crucial role in modulating TLR4 signaling pathways, influencing immune cell dynamics, and contributing to chemoresistance. These ncRNAs facilitate tumor-promoting processes, including macrophage polarization, dendritic cell suppression, and T-cell regulation, effectively establishing an immunosuppressive tumor microenvironment that further enhances therapeutic resistance. A comprehensive understanding of the complex interplay between TLR4 and ncRNAs unveils potential avenues for identifying predictive biomarkers and discovering novel therapeutic targets in cancer. Future research initiatives should prioritize the development of personalized therapeutic strategies that specifically target TLR4 signaling and its ncRNA regulators to counteract drug resistance and improve clinical outcomes. This review extensively evaluates the role of TLR4 in cancer biology, emphasizing its critical importance in developing innovative cancer management strategies.

Nasopharyngeal carcinoma (NPC) is a head and neck cancer with a high propensity for early metastatic spread. Emerging evidence shows that extracellular vesicles (EVs) are key players in cancer metastasis, but their role in NPC metastasis remains poorly understood. We here present the first description of the proteomic and functional profiles of serum-derived circulating small EVs in metastatic NPC patients. To enhance the capture of low-abundance signaling proteins in EVs, timsTOF-based four-dimensional label-free quantitative proteomics was employed. We found that metastatic NPC patients (M-NPC-EVs) exhibited the highest serum EV levels compared to locoregional patients (L-NPC-EVs) and healthy subjects (Normal-EVs). The proteome of M-NPC-EVs differed substantially from L-NPC-EVs and was functionally enriched in pathways regulating cell polarity and motility, glucose metabolism, and angiogenesis. Functional assays testing individual EV samples demonstrated that M-NPC-EVs pronouncedly enhanced NPC cell migration, invasion, and the formation of lamellipodia and filopodia in vitro, and promoted angiogenesis in subcutaneous Matrigel plugs in vivo. In silico analyses suggested that PTPRA, TPI1 and GPI highly enriched in M-NPC-EVs were putative drivers underlying the motogenic and angiogenic activities of M-NPC-EVs, and their high expression levels were associated with a poor prognosis of NPC patients. The increased expression of PTPRA, TPI1 and GPI in M-NPC-EVs was then validated in an independent cohort consisting of 175 NPC patients (locoregional n = 114; metastatic n = 61). Together, utilizing patient-derived EVs, we mimicked the potential pro-metastatic functions of EVs in NPC patients in vitro and in vivo and provided novel insights into their bioactive cargoes.

Papillary thyroid carcinoma (PTC) accounts for about 85% of thyroid cancer cases. Transmembrane protein 252 (TMEM252) is a gene encoding a transmembrane protein that has only been reported to be associated with triple-negative breast cancer. Herein, we first elucidated the physiological roles and possible regulatory proteins of TMEM252 in PTC pathogenesis.

Quantitative real-time polymerase chain reaction, western blot, and immunohistochemical analyses were utilized to ascertain the relative TMEM252 expression in PTC and surrounding normal tissues. Functional investigations involved CCK-8 viability assay, EdU incorporation assay for proliferation, transwell assays for migration and invasion, and an in vivo tumor development assessment to evaluate the TMEM252-mediated regulation of tumor formation.

Our results first revealed diminished TMEM252 transcript and protein expressions in PTC tissues and cell lines. TMEM252 overexpression suppressed cell proliferation through reducing p53, p21, and p16 expression. Conversely, TMEM252 depletion has opposite effects in PTC cells both in vivo. Additionally, the upregulation of TMEM252 demonstrated cell migration and invasion suppression by impeding the epithelial-mesenchymal transition (EMT) process via inhibition of the Notch pathway. Furthermore, overexpression of TMEM252 suppressed tumor growth in vivo.

Our study elucidates that TMEM252 suppresses PTC progression by modulating the Notch pathway. These findings underscore TMEM252 is a potential therapeutic target in managing PTC.

One of the most highly induced genes in zebrafish (Danio rerio) larvae after infection with the nodavirus red-spotted grouper nervous necrosis virus (RGNNV) was a member of the immunoglobulin superfamily (IgSF), which has remained uncharacterized and erroneously annotated in zebrafish and other fish species as galectin 17 (lgals17). We characterized this gene and named it immunoglobulin (Ig)-like domain-containing protein (igldcp), a new member of the IgSF that does not possess orthologs in mammals. Igldcp expression is induced by viral infection and it belongs to the group of interferon-stimulated genes (ISGs). In vitro overexpression of igldcp decreased RGNNV replication, whereas in vivo knockdown of this gene had the opposite effect, resulting in increased larval mortality. RNA-Seq analyses of larvae overexpressing igldcp in the absence or presence of infection with RGNNV showed that the main processes affected by Igldcp could be directly involved in the regulation of various cellular processes associated with the modulation of the immune system.

Breast cancer (BC) is a heterogeneous disease with multifactorial origins, including environmental, genetic, and immunological factors. Inflammatory cytokines, such as alpha 1 antitrypsin (α1-AT), are increased in BC and affect physiological and pathological conditions. This study aimed to evaluate the serum levels of α1-AT and perform a computational analysis of SERPINA1 in BC, as well as their association with molecular subtypes and clinical features.

For the experimental analysis, we evaluated 255 women with BC and 53 healthy women (HW) in a cross-sectional study. Molecular subtypes were identified by immunohistochemistry and TNM was used for clinical staging. Soluble levels of α1-AT were quantified by ELISA. Computational analysis of SERPINA1 expression was performed using GEPIA and cBioPortal.

α1-AT was increased in BC women versus HW (75.8 ng/mL vs. 532.2 ng/mL). Luminal A had higher concentration (547.5 ng/mL) than Triple Negative (TN) (484.1 ng/mL), but the levels were not associated with clinical stage. The computational analysis showed that SERPINA1 is overexpressed in BC with differential expression among subtypes; its overexpression is associated with a better prognosis, longer disease-free survival, and overall survival.

α1-AT levels are increased in women with BC women compared to HW. The Luminal A subtype shows higher soluble protein levels than the TN one. Furthermore, SERPINA1 mRNA overexpression in BC is linked to a protective effect.

Stomach adenocarcinoma (STAD) represents a significant global health burden, accounting for a considerable proportion of cancer-related mortalities, and NUAK1, a protein kinase, plays a crucial role in cellular metabolism, cell cycle regulation, migration, and tumor progression. However, its relationship with prognosis and immune infiltration in STAD has not been thoroughly investigated.

RNA sequencing data from the Cancer Genome Atlas (TCGA) and Genotypic Tissue Expression Project (GTEx) databases were employed to assess disparities in NUAK1 expression between STAD tumour and normal tissues. Additionally, we investigated the correlation between NUAK1 expression and patient prognosis, in addition to the level of immune cell infiltration. The potential functions were elucidated through an examination of the Gene Ontology (GO) Encyclopedia, the Kyoto Encyclopedia of Genes and Genomes (KEGG), and an enrichment analysis (GSEA). The GeneMANIA was used to validate the functions of nuak1-related genes.

Our analysis demonstrated that NUAK1 expression in tumour tissues exhibited a notable disparity from that observed in normal tissues, with elevated levels detected in STAD tissues. We used the GeneMANIA database to identify functionally similar genes with significantly higher expression for some genes in the unpaired group samples. An elevated NUAK1 expression level was found to correlate with a poorer overall survival (OS), disease-specific survival (DSS), and progression-free intervals (PFI). Additionally, immune infiltration analysis indicated a significant positive correlation between NUAK1 expression and various tumor-infiltrating immune cells, while a negative correlation was observed with T helper cell 17(Th17) cells. Furthermore, enrichment analysis was conducted to identify relevant biological features and pathways.

The expression levels of NUAK1 are significantly increased in STAD, and this heightened expression correlates with diminished OS, DSS, and PFI among affected patients. These observations indicate that NUAK1 has the potential to function as a prognostic biomarker for STAD and may represent a viable therapeutic target for intervention in its management.

Polyetheretherketone (PEEK), bearing an elastic modulus that effectively simulates the innate properties of natural bone, has come into the spotlight as a promising bone substitute material. Nonetheless, the biologically inert nature of PEEK, combined with its insubstantial osseointegration and sterilization capabilities, pose constraints on its clinical application in the realm of implants. RNA interference (RNAi), an effective technique used for gene expression regulation, has begun to be applied in implant surface modification. Herein, siCKIP-1 is securely affixed to the surface of PEEK implants, aided by an antibacterial polyphenol tannic acid (pTAN) coatings, enhancing physiologic osseointegration and inhibiting bacterial infection. This method breakthrough not merely facilitates the convenience, but also multifaceted PEEK implants' refinements. The modified PEEK implants have impressive biocompatibility coupled with a noteworthy degree of antibacterial properties. Meanwhile, modified PEEK implants improved osteogenic differentiation of rat bone mesenchymal stem cells (rBMSCs) and demonstrated excellent osteointegrative properties in rat femur implantation models. Therefore, identifying a new implant material with excellent biocompatibility and biomechanical properties is essential.

Esophageal squamous cell carcinoma (ESCC) is characterized by high invasiveness and poor prognosis. The role of Sorbin and SH3 domain-containing protein 2 (SORBS2) in ESCC remains largely unexplored.

The expression levels of SORBS2 in ESCC were detected using RNA-seq and proteomics data. The biological functions of SORBS2 in ESCC were investigated through in vivo and in vitro experiments. The mechanism of SORBS2 was explored using RIP-seq technology, which identified the key downstream molecule metalloproteinase-3 (TIMP3). The interaction between SORBS2 and TIMP3, including specific binding sites, was validated through RIP-qPCR and RNA pull-down assays. The impact of altered SORBS2 expression in ESCC on HUVECs was assessed using endothelial tube formation assays.

SORBS2 expression was significantly downregulated in ESCC tissues, and its decreased expression was associated with poor prognosis. Overexpression of SORBS2 in ESCC cell lines inhibited cell proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, SORBS2 bound to the 3' UTR of TIMP3 mRNA, enhancing its stability and thereby regulating TIMP3 expression. Rescue experiments demonstrated that increased TIMP3 expression could reverse the promotive effects of SORBS2 knockdown on ESCC, confirming TIMP3 as a critical downstream molecule of SORBS2. Furthermore, downregulation of SORBS2 in ESCC cells was associated with activation of HUVEC functions, whereas upregulation of TIMP3 could reverse this effect. The SORBS2/TIMP3 axis may exert tumor suppressive effects by influencing extracellular matrix degradation.

This study confirms that SORBS2 inhibits ESCC tumor progression by regulating extracellular matrix degradation through TIMP3, providing a potential therapeutic target for future treatment interventions.

Triple-negative breast cancer (TNBC) is a highly aggressive and invasive form of breast cancer (BC) with a high mortality rate and a lack of effective targeted drugs. Family with sequence similarity 83 member H (FAM83H) is critically implicated in tumorigenesis. However, the potential role of FAM83H in TNBC remains elusive. Here, we discovered that FAM83H exhibited high expression in tumor tissues of patients with TNBC and was associated with TNM stage. Gain- or loss-of-function experiments were conducted to explore the biological role of FAM83H in TNBC. Subsequently, functional enrichment analysis confirmed that FAM83H overexpression promoted TNBC cell proliferation, invasion, migration and epithelial-mesenchymal transition (EMT), accompanied by upregulation of cyclin E, cyclin D, Vimentin, N-cadherin and Slug. As observed, FAM83H knockdown showed anti-cancer effects, such as fostering apoptosis and inhibiting tumorigenicity and metastasis of TNBC cells. Mechanistically, FAM83H activated the NF-κB signaling pathway. Moreover, a dual-luciferase reporter assay demonstrated that GLIS family zinc finger 3 (GLIS3) bound to the promoter of FAM83H and enhanced its transcription. Notably, overexpression of GLIS3 significantly stimulated TNBC cell proliferation and invasion, and all of this was reversed by rescue experiments involving the knockdown of FAM83H. Overall, FAM83H exacerbates tumor progression, and in-depth understanding of FAM83H as a therapeutic target for TNBC will provide clinical translational potential for intervention therapy.

Epithelial-Mesenchymal Transition (EMT) is a fundamental biological process involved in embryonic development, wound healing, and cancer progression. In lung cancer, EMT is a key regulator of invasion and metastasis, significantly contributing to the fatal progression of the disease. Age-related factors such as cellular senescence, chronic inflammation, and epigenetic alterations exacerbate EMT, accelerating lung cancer development in the elderly. This review describes the complex mechanism among EMT and age-related pathways, highlighting key regulators such as TGF-β, WNT/β-catenin, NOTCH, and Hedgehog signalling. We also discuss the mechanisms by which oxidative stress, mediated through pathways involving NRF2 and ROS, telomere attrition, regulated by telomerase activity and shelterin complex, and immune system dysregulation, driven by alterations in cytokine profiles and immune cell senescence, upregulate or downregulate EMT induction. Additionally, we highlighted pathways of transcription such as SNAIL, TWIST, ZEB, SIRT1, TP53, NF-κB, and miRNAs regulating these processes. Understanding these mechanisms, we highlight potential therapeutic interventions targeting these critical molecules and pathways.

Esophageal carcinoma (EC) is one of the most common tumors in China and seriously affects patient survival and quality of life. In recent years, increasing studies have shown that the tumor microenvironment is crucial in promoting tumor progression and metastasis. Tumor-associated macrophages (TAM) are key components of the tumor immune microenvironment and promote both tumor growth and antitumor immunity. Much evidence suggests that TAMs are closely associated with esophageal tumors. However, understanding of the clinical value and mechanism of action of TAM in esophageal cancer remains limited. Therefore, we reviewed the status of research on the role and mechanism of action of TAM in EC progression and summarized its potential clinical application value to provide a theoretical basis for the clinical treatment of EC.

The tumor microenvironment (TME) plays a crucial role in tumor progression and immunoregulation. Major histocompatibility complex class II (MHC-II) is essential for immune surveillance within the TME. While MHC-II genes are typically expressed by professional antigen-presenting cells, they are also expressed in tumor cells, potentially facilitating antitumor immune responses. To understand the role of MHC-II-expressing tumor cells, we analyzed triple-negative breast cancer (TNBC), an aggressive subtype with poor prognosis and limited treatment options, using public bulk RNA-seq, single-cell RNA-seq, and spatial transcriptomics datasets. Our analysis revealed a distinct tumor subpopulation that upregulates MHC-II genes and actively interacts with immune cells. We implicated that this subpopulation is preferentially present in proximity to regions in immune infiltration of TNBC patient cohorts with a better prognosis, suggesting the functional importance of MHC-II-expressing tumor cells in modulating the immune landscape and influencing patient survival outcomes. Remarkably, we identified a prognostic signature comprising 40 significant genes in the MHC-II-expressing tumors in which machine leaning models with the signature successfully predicted patient survival outcomes and the degree of immune infiltration. This study advances our understanding of the immunological basis of cancer progression and suggests promising new directions for therapeutic strategies.

Breast cancer is the leading cause of cancer-related morbidity and mortality among women worldwide, with bone being the most common site of all metastatic breast cancer. Bone metastases are often associated with pain and skeletal-related events (SREs), indicating poor prognosis and poor quality of life. Most current therapies for breast cancer bone metastasis primarily serve palliative purposes, focusing on pain management, mitigating the risk of bone-related complications, and inhibiting tumor progression. The emergence of nanodelivery systems offers novel insights and potential solutions for the diagnosis and treatment of breast cancer-related bone metastasis. This article reviews the recent advancements and innovative applications of nanodrug delivery systems in the context of breast cancer bone metastasis and explores future directions in nanotheranostics.

The development of tumors and their metastasis relies heavily on the process of angiogenesis. When the volume of a tumor expands, the resulting internal hypoxic conditions trigger the body to enhance the production of various angiogenic factors. These include vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), and transforming growth factor-α (TGF-α), all of which work together to stimulate the activation of endothelial cells and catalyze angiogenesis. Antiangiogenic therapy (AAT) aims to normalize tumor blood vessels by inhibiting these angiogenic signals. In this review, we will explore the molecular mechanisms of angiogenesis within the tumor microenvironment, discuss traditional antiangiogenic drugs along with their limitations, examine new antiangiogenic drugs and the advantages of combination therapy, and consider future research directions in the field of antiangiogenic drugs. This comprehensive overview aims to provide insights that may aid in the development of more effective anti-tumor treatments.

The tumor microenvironment (TME) encompasses the complex and diverse surroundings in which tumors arise. Emerging insights highlight the TME's critical role in tumor development, progression, metastasis, and treatment response. Consequently, the TME has attracted significant research and clinical interest, leading to the identification of numerous novel therapeutic targets. Advances in molecular technologies now enable detailed genomic and transcriptional analysis of cancer cells and the TME and the integration of microenvironmental data to the tumor genomic landscape. This comprehensive review discusses current progress in targeting the TME for drug development, addressing associated challenges, strategies for modulating the pro-tumor microenvironment, and the discovery of new targets.

Aminopeptidases are exopeptidases that catalyze the cleavage of amino acid residues from the N-terminal fragment of protein or peptide substrates. Owing to their function, they play important roles in protein maturation, signal transduction, cell-cycle control, and various disease mechanisms, notably in cancer pathology. To gain better insights into their function, molecular imaging assisted by fluorescence and bio/chemiluminescence probes has become an indispensable method to their superiorities, including excellent sensitivity, selectivity, and real-time and noninvasive imaging. Numerous efforts are made to develop activatable probes that can effectively enhance efficiency and accuracy as well as minimize the side effects. This review is classified according to the type of aminopeptidases, summarizing some recent works on the design, work mechanism, and sensing, imaging, and theranostic performance of their activatable probe. Finally, the current challenges are outlined in developing activatable probes for aminopeptidases and provide possible solutions for future advancements.

Circular RNAs play a pivotal role in the progression of various cancers. In our previous study, we observed high expression of the circRNA MALAT1 (cMALAT1) in intrahepatic cholangiocarcinoma (ICC) cells co-incubated with activated hepatic stellate cells. This study is designed to explore the roles of cMALAT1 and the underlying mechanisms in ICC. We find that cMALAT1 significantly facilitates the progression of ICC both in vitro and in vivo. The binding between cMALAT1 and miR-512-5p is subsequently confirmed through RNA pull-down experiments. As anticipated, the application of miR-512-5p mimics noticeably reverses the cMALAT1 overexpression-induced malignant phenotypes of ICC cells. Furthermore, VCAM1 is identified as a downstream gene of the cMALAT1/miR-512-5p axis. Importantly, silencing of VCAM1 not only effectively suppresses the malignant phenotypes of ICC cells but also significantly impairs the functions of cMALAT1. Our study reveals that cMALAT1 promotes the progression of ICC by competitively binding to VCAM1 mRNA with miR-512-5p, leading to the upregulation of VCAM1 expression and the activation of the PI3K/AKT signaling pathway.

Type 1 diabetes mellitus (T1DM) is a chronic condition primarily managed with insulin replacement, leading to significant treatment costs. Complications include vasculopathy, cardiovascular diseases, nephropathy, neuropathy, and reticulopathy. Pancreatic islet transplantation is an option but its success does not depend solely on adequate vascularization. The main limitations to clinical islet transplantation are the scarcity of human pancreas, the need for immunosuppression, and the inadequacy of the islet isolation process. Despite extensive research, T1DM remains a major global health issue. In 2015, diabetes affected approximately 415 million people, with projected expenditures of USD 1.7 trillion by 2030. Pancreas transplantation faces challenges due to limited organ availability and complex vascularization. T1DM is caused by the autoimmune destruction of insulin-producing pancreatic cells. Advances in biomaterials, particularly the extracellular matrix (ECM), show promise in tissue reconstruction and transplantation, offering structural and regulatory functions critical for cell migration, differentiation, and adhesion. Tissue engineering aims to create bioartificial pancreases integrating insulin-producing cells and suitable frameworks. This involves decellularization and recellularization techniques to develop biological scaffolds. The challenges include replicating the pancreas's intricate architecture and maintaining cell viability and functionality. Emerging technologies, such as 3D printing and advanced biomaterials, have shown potential in constructing bioartificial organs. ECM components, including collagens and glycoproteins, play essential roles in cell adhesion, migration, and differentiation. Clinical applications focus on developing functional scaffolds for transplantation, with ongoing research addressing immunological responses and long-term efficacy. Pancreatic bioengineering represents a promising avenue for T1DM treatment, requiring further research to ensure successful implementation.

The journey of cancer development is a multifaceted and staged process. The array of treatments available for cancer varies significantly, dictated by the disease's type and stage. Cancer-associated fibroblasts (CAFs), prevalent across various cancer types and stages, play a pivotal role in tumor genesis, progression, metastasis, and drug resistance. The strategy of concurrently targeting cancer cells and CAFs holds great promise in cancer therapy. In this review, we focus intently on CAFs, delving into their critical role in cancer's progression. We begin by exploring the origins, classification, and surface markers of CAFs. Following this, we emphasize the key cytokines and signaling pathways involved in the interplay between cancer cells and CAFs and their influence on the tumor immune microenvironment. Additionally, we examine current therapeutic approaches targeting CAFs. This article underscores the multifarious roles of CAFs within the tumor microenvironment and their potential applications in cancer treatment, highlighting their importance as key targets in overcoming drug resistance and enhancing the efficacy of tumor therapies.

Distant metastasis is a primary cause of mortality and contributes to poor surgical outcomes in cancer patients. Before the development of organ-specific metastasis, the formation of a pre-metastatic niche is pivotal in promoting the spread of cancer cells. This review delves into the intricate landscape of the pre-metastatic niche, focusing on the roles of tumor-derived secreted factors, extracellular vesicles, and circulating tumor cells in shaping the metastatic niche. The discussion encompasses cellular elements such as macrophages, neutrophils, bone marrow-derived suppressive cells, and T/B cells, in addition to molecular factors like secreted substances from tumors and extracellular vesicles, within the framework of pre-metastatic niche formation. Insights into the temporal mechanisms of pre-metastatic niche formation such as epithelial-mesenchymal transition, immunosuppression, extracellular matrix remodeling, metabolic reprogramming, vascular permeability and angiogenesis are provided. Furthermore, the landscape of pre-metastatic niche in different metastatic organs like lymph nodes, lungs, liver, brain, and bones is elucidated. Therapeutic approaches targeting the cellular and molecular components of pre-metastatic niche, as well as interventions targeting signaling pathways such as the TGF-β, VEGF, and MET pathways, are highlighted. This review aims to enhance our understanding of pre-metastatic niche dynamics and provide insights for developing effective therapeutic strategies to combat tumor metastasis.

The liver is one of the most common sites for metastasis, which involves the spread from primary tumors to surrounding organs and tissues in the human body. There are a few steps in cancer expansion: invasion, inflammatory processes allowing the hepatic niche to be created, adhesions to ECM, neovascularization, and secretion of enzymes. The spread of tumor cells depends on the microenvironment created by the contribution of many biomolecules, including proteolytic enzymes, cytokines, growth factors, and cell adhesion molecules that enable tumor cells to interact with the microenvironment. Moreover, the microenvironment plays a significant role in tumor growth and expansion. The secreted enzymes help cancer cells facilitate newly formed hepatic niches and promote migration and invasion. Our study discusses pharmacological methods used to prevent liver metastasis by targeting the tumor microenvironment and cancer cell colonization in the liver. We examine randomized studies focusing on median survival duration and median overall survival in patients administered placebo compared with those treated with bevacizumab, ramucirumab, regorafenib, and ziv-aflibercept in addition to current chemotherapy. We also include research on mice and their responses to these medications, which may suppress metastasis progression. Finally, we discuss the significance of non-pharmacological methods, including surgical procedures, radiotherapy, cryotherapy, radiofrequency ablation (RFA), and transarterial embolization (TAE). In conclusion, the given methods can successfully prevent metastases to the liver and prolong the median survival duration and median overall survival in patients suffering from cancer.

Metastasis has been one of the primary reasons for the high mortality rates associated with tumours in recent years, rendering the treatment of current malignancies challenging and representing a significant cause of recurrence in patients who have undergone surgical tumour resection. Halting tumour metastasis has become an essential goal for achieving favourable prognoses following cancer treatment. In recent years, increasing clarity in understanding the mechanisms underlying metastasis has been achieved. The concept of premetastatic niches has gained widespread acceptance, which posits that tumour cells establish a unique microenvironment at distant sites prior to their migration, facilitating their settlement and growth at those locations. Neutrophils serve as crucial constituents of the premetastatic niche, actively shaping its microenvironmental characteristics, which include immunosuppression, inflammation, angiogenesis and extracellular matrix remodelling. These characteristics are intimately associated with the successful engraftment and subsequent progression of tumour cells. As our understanding of the role and significance of neutrophils in the premetastatic niche deepens, leveraging the presence of neutrophils within the premetastatic niche has gradually attracted the interest of researchers as a potential therapeutic target. The focal point of this review revolves around elucidating the involvement of neutrophils in the formation and shaping of the premetastatic niche (PMN), alongside the introduction of emerging therapeutic approaches aimed at impeding cancer metastasis.