The Emerging Roles of TRPV4 in Cancer
N. N. Bahari1, S. Y. N. Jamaludin1, A. H. Jahidin2, M. N. Zahary3, A. B. Mohd Hilmi3, N. H. A. Bakar1 and A. M. Ali4

1Faculty of Medicine, Universiti Sultan Zainal Abidin, Medical Campus, Terengganu, Malaysia.

2Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, Selangor, Malaysia.

3Faculty of Health Sciences, Universiti Sultan Zainal Abidin, Gong Badak Campus, Terengganu, Malaysia.

4Faculty of Bioresources and Food Industry, Universiti Sultan Zainal Abidin, Besut Campus, Terengganu, Malaysia.

Corresponding Author E-mail: yusrinanadihah@unisza.edu.my

Abstract: Cancer is a disease with marked heterogeneity in both response to therapy and survival. Malignant neoplasm or cancer is a type of genetic disease in which a group of cells display uncontrolled growth, invasion and sometimes metastasis. Cancer progression is not only associated with changes in the cell cycle that inactivate pathways leading to cell death or senescence but also enhanced cell proliferation. Usually, these changes are associated with alterations in Ca2+ homeostasis in cells. The transient receptor potential (TRP) channels play a role as cell sensors and are involved in a plethora of Ca2+-mediated cell functions. TRP vanilloid 4 (TRPV4) is a member of the TRPV ion channel family which is permeable to both Ca2+ and Na+. TRPV4 is expressed in various types of tissues such as kidneys, airway smooth muscle and lungs. As other TRPV channels, TRPV4 may also be involved in cancer cell proliferation, apoptosis, angiogenesis, migration and invasion. Previous studies have demonstrated that TRPV4 plays a role in the proliferation of several types of cancer cells. Moreover, TRPV4 also contributes to cancer cell angiogenesis via arachidonic acid-induced migration of breast tumour-derived endothelial cells. TRPV4 is also able to regulate angiogenesis via mechanotransduction. Recent studies have also reported a significant role of TRPV4 in breast cancer metastasis and induction of breast cancer cell death. In this review, the emerging roles of TRPV4 in cancer will be discussed which further supports the potential of TRPV4 as a promising drug target for cancer therapy.

Keywords: TRPV4; cancer; Proliferation; Angiogenesis; Metastasis; Apoptosis

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