The Role of Transient Receptor Potential Cation Channel subfamily V member 4 (TRPV4) in Colorectal Cancer

Siti Yusrina Nadihah, Jamaludin and Mohd Hilmi, Abu Bakar and Mohd Nizam, Zahary and Aisyah Hasyila, Jahidin and Nurul Nadiah, Bahari (2019) The Role of Transient Receptor Potential Cation Channel subfamily V member 4 (TRPV4) in Colorectal Cancer. In: 2019 - 28th International Conference on Research in Life-Sciences & Healthcare (ICRLSH), 30-31 December 2019, The Regency Scholar's Hotel, Universiti Teknologi Malaysia (UTM) Kuala Lumpur.

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Abstract

The transient receptor potential cation channel subfamily V member 4 (TRPV4) is a non-selective calcium (Ca2+)-permeable channel which is expressed in many types of tissues. In addition to its roles in various physiological processes such as osmoregulation and mechanosensation, growing evidence suggests that TRPV4 is also involved in several aspects of tumourigenesis. Despite the reported roles of TRPV4 in several types of cancers, the role of TRPV4 in colorectal cancer has not been extensively assessed. This study aimed at exploring the potential role of TRPV4 in colorectal cancer cells. Quantitative real-time PCR analysis showed that TRPV4 mRNA levels were lower in HT-29 colorectal cancer cells than normal colon CCD-18Co cells. In contrast, TRPV4 mRNA was undetected in HCT-116 colorectal cancer cells. Pharmacological activation of TRPV4 using GSK1016790A promoted the proliferation of HT-29 cells while TRPV4 inhibition using RN 1734 decreased their proliferation, as assessed by the MTT cell proliferation assay. Cotreatment with RN 1734 attenuated GSK1016790A-induced increases in proliferation in HT-29 cells. Cell cycle analysis by flow cytometry revealed that pharmacological modulation of TRPV4 had no pronounced effect on the cell cycle progression in HT-29 cells. Analysis from the AnnexinV/PI double-staining assay demonstrated that both activation and inhibition of TRPV4 channel could promote the death of HT-29 cells, despite at different degrees of cell death induction. Altogether, these findings suggest divergent TRPV4 mRNA expression levels between human colorectal cancer cells and normal colon cells. Pharmacological modulation of TRPV4 appears to alter the proliferation of HT-29 cells and induces cell death in this cell line. TRPV4 may represent a promising drug target for the treatment of colorectal cancer.

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