Abstract
The goal of this article is to provide a critical review of the transient receptor potential melastatin-subfamily member 8 (TRPM8) in cancers, with an emphasis on its roles in cellular proliferation, survival, and invasion. The TRPM8 ion channels regulate Ca2+ homeostasis and function as a cellular sensor and transducer of cold temperature. Accumulating evidence has demonstrated that TRPM8 is aberrantly expressed in a variety of malignant solid tumors. Clinicopathological analysis has shown that over-expression of TRPM8 correlates with tumor progression. Experimental data have revealed important roles of TRPM8 channels in cancer cells proliferation, survival, and invasion, which appear to be dependent on the cancer type. Recent reports have begun to reveal the signaling mechanisms that mediate the biological roles of TRPM8 in tumor growth and metastasis. Determining the mechanistic roles of TRPM8 in cancer is expected to elucidate the impact of thermal and chemical stimuli on the formation and progression of neoplasms. Translational research and clinical investigation of TRPM8 in malignant diseases will help exploit these ion channels as molecular biomarkers and therapeutic targets for developing precision cancer medicine.
Highlights
This article focuses on the transient receptor potential melastatin-subfamily member 8 (TRPM8) ion channel in cancers, with an emphasis on its roles in proliferation, survival, and invasion
Experimental data implicate that TRPM8 channels play important roles in cancer cells proliferation, survival, migration, invasion, and neurosecretion
Expression of TRPM8 in breast carcinoma correlates with histological grade, Ki-67, tumor size, and expression of estrogen receptor. These findings suggest that TRPM8 channels play a role in the development and growth of mammary tumor [52,53,54]
Summary
This article focuses on the transient receptor potential melastatin-subfamily member 8 (TRPM8) ion channel in cancers, with an emphasis on its roles in proliferation, survival, and invasion. The prostate kallikrein, prostate-specific antigen (PSA), increases expression of TRPM8 channels on the plasma membrane and enhances coolness-induced TRPM8-mediated current through the bradykinin 2 receptor signaling pathway [31]. These data suggest that PSA is a physiological agonist of TRPM8. The TRPM8 channel activity can be influenced by physical and chemical alterations in the microenvironment, whereas PIP2, changes in pH, PKC/PKA signaling, PSA, and TCAFs modulate the response of TRPM8 to cold temperature and cooling agents. The various roles of TRPM8 in cancer including proliferation, survival, and invasion are reviewed
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