<p>TRPV4 Overexpression Promotes Metastasis Through Epithelial–Mesenchymal Transition in Gastric Cancer and Correlates with Poor Prognosis</p>

Abstract

Transient receptor potential vanilloid 4 (TRPV4) has been reported to be involved in the progression of several human tumors. Nevertheless, clinical significance and molecular mechanism of TRPV4 in gastric cancer (GC) remain poorly defined. Patients and Methods: Immunohistochemistry assays were used to investigate the correlation between the expression of TRPV4 and epithelial-mesenchymal transition (EMT) markers in human GC tissues. The correlations between TRPV4 expression and clinicopathological features and between TRPV4 expression and survival rates were also examined. TRPV4 knockdown was performed by using small interfering RNAs. In vitro, Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and transwell assay were employed to further explore the biological functions of TRPV4, and Western blotting was used to evaluate the changes in the expression of TRPV4 protein and EMT-related proteins in HGC-27 and MGC-803 human GC cell lines. Results: TRPV4 expression was upregulated in GC tissues and cell lines. TRPV4 overexpression was associated with greater depth of tumor invasion, lymph node metastasis, higher TNM stage, poor overall survival, and worse disease-free survival. TRPV4 expression was inversely correlated with E-cadherin expression and positively correlated with vimentin expression. In vitro, knockdown of TRPV4 inhibited GC cell proliferation, colony formation, and invasion. Furthermore, the knockdown of TRPV4 modulated EMT by upregulating E-cadherin expression and downregulating the expression of N-cadherin and vimentin. In addition, the EMT-related transcription factor Snail was downregulated, whereas the expression levels of other transcription factors such as Slug and Twist did not change. Conclusion: TRPV4 was upregulated in human GC and the overexpression of TRPV4 could promote GC progression, partially through Snail-mediated EMT.

Expression Profiles of ASIC1/2 and TRPV1/4 in Common Skin Tumors

“…Huang et al activated TRPV4 in esophageal SCC, which resulted in cellular migration of the tumor cells [ 30 ]. Additionally, in gastric cancer TRPV4 is upregulated and is even associated with higher tumor invasion, lymph node metastasis and poor survival [ 31 ]. Contradictory to our results, another research group detected a downregulation of TRPV4 in specific NMSC, as Bowen’s disease (BD), solar keratosis (SK), and also BCC and SCC [ 15 ].…”

FAST1 Predicts Poor Survival of Renal Carcinoma and Promotes Its Progression Through the TGF-β/Smad Pathway

“…23 In terms of its functions, EMT plays a vital role in modulating embryonic development, wound healing, cancer cell metastasis, and drug resistance. [24][25][26][27] It is worth noting that in non-small cell lung cancer (NSCLC), UBE2T enhances the degradation of FOXO1 in a ubiquitination-dependent manner, thus repressing EMT of NSCLC cells. 28 Similarly, this study found that FAST1 up-regulation led to up-regulated N-cadherin and Snail but inhibited E-cadherin and…”

TRPV4 is a Prognostic Biomarker That Correlates With the Immunosuppressive Microenvironment and Chemoresistance of Anti-Cancer Drugs

“…Moreover, the functions of TRPV4 are different or even opposite in different tumors. TRPV4 plays an oncogenic role in breast cancer, endometrial cancer, gastric cancer, oral squamous cell carcinoma, and COAD [2,[9][10][11][12] and a suppressor gene role in glioma [1]. However-in many other tumor types-the function of TRPV4 remains unclear.…”