TRPV4 Channels Mediate Bladder Cancer Cell Proliferation, Migration and Chemoresistance

Area of Science:

• Oncology
• Molecular Biology
• Urology

Background:

• Bladder cancer (BLCA) is a prevalent malignancy with limited treatment advancements.
• The role of Transient Receptor Potential Vanilloid type 4 (TRPV4) in BLCA pathogenesis remains largely unexplored.

Purpose of the Study:

• To investigate TRPV4 expression in BLCA tissues and its functional role in cancer cell proliferation, migration, and chemoresistance.
• To evaluate TRPV4 as a potential therapeutic target for BLCA.

Main Methods:

• Bioinformatic analysis of TRPV4 expression in BLCA databases (UALCAN, cBioPortal).
• Functional assays using normal human urothelial (SV-HUC-1) and BLCA (T-24, UM-UC-3) cells to assess calcium influx, cell proliferation, migration, and response to TRPV4 inhibition and cisplatin treatment.

Main Results:

• TRPV4 expression is significantly elevated in BLCA tissues, particularly in early-stage and muscle-invasive bladder cancer (MIBC).
• Enhanced TRPV4-mediated calcium influx, increased cell proliferation, and migration were observed in BLCA cells compared to normal cells.
• Pharmacological inhibition of TRPV4 reduced BLCA cell proliferation and migration.
• TRPV4 was downregulated by cisplatin in chemosensitive cells but not in chemoresistant cells, suggesting a role in chemoresistance.

Conclusions:

• TRPV4 is a critical driver of BLCA progression, influencing cell proliferation and migration.
• TRPV4 may play a significant role in conferring resistance to chemotherapy.
• Targeting TRPV4 presents a promising novel therapeutic strategy for bladder cancer treatment and overcoming drug resistance.