Transient receptor potential ion-channel subfamily V member 4: a potential target for cancer treatment

Abstract

The transient receptor potential ion-channel superfamily consists of nonselective cation channels located mostly on the plasma membranes of numerous animal cell types, which are closely related to sensory information transmission (e.g., vision, pain, and temperature perception), as well as regulation of intracellular Ca 2+ balance and physiological activities of growth and development. Transient receptor potential ion channel subfamily V (TRPV) is one of the largest and most diverse subfamilies, including TRPV1-TRPV6 involved in the regulation of a variety of cellular functions. TRPV4 can be activated by various physical and chemical stimuli, such as heat, mechanical force, and phorbol ester derivatives participating in the maintenance of normal cellular functions. In recent years, the roles of TRPV4 in cell proliferation, differentiation, apoptosis, and migration have been extensively studied. Its abnormal expression has also been closely related to the onset and progression of multiple tumors, so TRPV4 may be a target for cancer diagnosis and treatment. In this review, we focused on the latest studies concerning the role of TRPV4 in tumorigenesis and the therapeutic potential. As evidenced by the effects on cancerogenesis, TRPV4 is a potential target for anticancer therapy. Facts 1. TRPV4 is a broadly expressed, nonselective calcium permeant cation channel that perform an important role in regulating the Ca 2+ influx in the cells in which they are expressed. 2. TRPV4 is a thermosensor, activated by temperatures greater than 24-27°C, also can be activated by osmotic, mechanical, and chemical cues. 3. TRPV4 is constitutively expressed and capable of spontaneous activity in the absence of agonist stimulation, which suggests that it serves important physiological functions. Open questions 1. What is the underlying cause of TRPV4 expression levels in different types of cancer? 2. Whether it is possible to lower the toxicity and highefficiency TRPV4 inhibitors from natural products to treat various diseases? 3. How to inhibit the development of cancer by targeting TRPV4 of tumor cells without affecting the function of normal cells?

Involvement of Neural Transient Receptor Potential Channels in Peripheral Inflammation

“…The pore loop is between segments 5 and 6 and both the C-and N-termini are located within the cytoplasm (31). The channel contains six ankyrin repeats and the phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP2), can bind to this site inhibiting the channel (32). Similar to TRPV1, TRPV4 is expressed on a variety of cells such as neurons, leukocytes (33), T cells (34), and macrophages (35).…”

Exploring the Therapeutic Potential of Membrane Transport Proteins: Focus on Cancer and Chemoresistance

“…Similarly, elevated levels of TRPV4 in breast, gastric, ovarian, and colon cancers correlates with increased cancer cell proliferation, invasion, and poor patient survival [214][215][216]. On the contrary, the expression level of TRPV4 is significantly reduced in advanced endothelial and skin cancers [211,217], suggesting that TRPV4 exhibits both oncogenic or tumour suppressor effects depend on the cancer type [218]. Moreover, TRPV5 was found downregulated in lung [219] and renal [220] tumours, and its reduced expression correlates with poor overall survival and short relapse-free survival of lung cancer patients [219].…”

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

“…Nowadays, there is an increasing interest in ion channels, especially the mechanosensitive ion channels, as potential drug targets in many types of cancers. [1][2][3][4] Transient receptor potential vanilloid 4 (TRPV4) is the vanilloid subfamily of the TRP channels, which is involved in mechanotransduction processes like volume regulation and osmosensing. 4 Mechanical stress is a critical mediator of cancer progression and mechanosensitive ion channels are functionally up-regulated in cancers that depend on Ca 2+ signaling.…”

“…[1][2][3][4] Transient receptor potential vanilloid 4 (TRPV4) is the vanilloid subfamily of the TRP channels, which is involved in mechanotransduction processes like volume regulation and osmosensing. 4 Mechanical stress is a critical mediator of cancer progression and mechanosensitive ion channels are functionally up-regulated in cancers that depend on Ca 2+ signaling. 3,5,6 Several studies demonstrated that TRPV4 was overexpressed in different types of cancers, including human colon cancer, breast cancer, and hepatocellular carcinoma, and was involved in cancer cell proliferation and migration.…”

“…3,5,6 Several studies demonstrated that TRPV4 was overexpressed in different types of cancers, including human colon cancer, breast cancer, and hepatocellular carcinoma, and was involved in cancer cell proliferation and migration. 4,[7][8][9] Thus far, only two studies demonstrated that activation of calcium-sensing receptor (CaSR) and vasoactive intestinal peptide receptor 1 (VPAC1) could promote gastric cancer cell progression through TRPV4-mediated Ca 2+ signaling. 10,11 In these studies, the expression of TRPV4 protein, as the downstream signal of CaSR and VPAC1, was detected in GC tissues and normal tissues in small biopsy samples.…”