Akademik Veri Yönetim Sistemi
JOURNAL OF BASIC AND CLINICAL HEALTH SCIENCES, cilt.9, sa.1, 2025 (ESCI)
Background: Epithelial-to-mesenchymal transition (EMT) enhances the invasive potential of cancers, significantly affecting survival rates in metastatic disease. TGF-3, a potent EMT regulator enriched in colon cancer (CRC), is influenced by bioelectric and biophysical forces. While some ion channels and mechanical forces are linked, TGF-3-coupled mechanosensing mechanisms in CRC remain poorly understood. This study investigates the mechanosensitive ion channel TRPV4 and its role in TGF-3induced EMT, focusing on channel trafficking and its functional implications in CRC. Methods: We analyzed mechanosensitive ion channels mRNA expressions in CRC stages and evaluated their association with survival through Kaplan-Meier analysis. Correlations were analyzed with mesenchymal gene sets, soluble factors, and TGF-3 signaling. Immunofluorescence was used to visualize TRPV4 localization in untreated and 10 ng/mL TGF-31-treated colon cell lines. Functional studies involved co-stimulation with TGF-31 and TRPV4 modulators (GSK101 and HC-067047) to assess EMT-related changes. Results: TRPV4 mRNA is elevated in CRC, with TRPV4-001 as the predominant isoform. High expression correlated with poor survival, EMT signatures, and TGF-31 signaling. TGF-31 induced out-of-nucleus TRPV4 translocation. TRPV4 inhibition reduced TGF-3-induced N-cadherin expression, mitigating EMT. Conclusion: TRPV4 regulates TGF-3-induced EMT through trafficking mechanisms. Its inhibition presents anti-metastatic potential, identifying TRPV4 as a therapeutic target in CRC.