TRPM8: a potential target for cancer treatment

Abstract

Transient receptor potential (TRP) cation channel superfamily plays critical roles in variety of processes, including temperature perception, pain transduction, vasorelaxation, male fertility, and tumorigenesis. One of seven families within the TRP superfamily of ion channels, the melastatin, or TRPM family comprises a group of eight structurally and functionally diverse channels. Of all the members of TRPM subfamily, TRPM8 is the most notable one. A lot of literatures have demonstrated that transient receptor potential melastatin 8 (TRPM8) could perform a myriad of functions in vertebrates and invertebrates alike. In addition to its well-known function in cold sensation, TRPM8 has an emerging role in a variety of biological systems, including thermoregulation, cancer, bladder function, and asthma. Recent studies have shown that TRPM8 is necessary to the initiation and progression of tumors, and the aberrant expression of TRPM8 was found in varieties of tumors, such as prostate tumor, melanoma, breast adenocarcinoma, bladder cancer, and colorectal cancer, making it a novel molecular target potentially useful in the diagnosis and treatment of cancer. This review outlines our current understanding on the role of TRPM8 in occurrence and development of different kinds of tumor and also includes discussion about the regulation of TRPM8 during carcinogenesis as well as therapeutic potential of targeting TRPM8 in tumor, which may be utilized for a potential pharmacological use as a target for anti-cancer therapy.

Transient Receptor Potential (TRP) Channels

“…In addition to thermosensation, TRPM8 has also been shown to be involved in pain sensation, thermoregulation, bladder function and cancer (Liu et al 2016). TRPM8 is a non-selective, Ca 2+ permeable, outwardly rectifying cation channel (McKemy 2007; Liu et al 2016). Of the TRPM subfamily, TRPM8 is the most selective for Ca 2+ with a selectivity ratio (P Ca /P Na ) of 3.3 (Zholos et al 2011).…”

“…This channel was originally cloned from a prostate cDNA library screen (Tsavaler et al 2001). It was found to be involved in prostate cancer, specifically there was found to be an androgen dependent overexpression of TRPM8 in androgen receptor positive prostate cancers (Liu et al 2016). TRPM8 is involved in a variety of other cancers including adenocarcinoma, melanomas, as well as lung and breast cancers (Liu et al 2016).…”

“…It was found to be involved in prostate cancer, specifically there was found to be an androgen dependent overexpression of TRPM8 in androgen receptor positive prostate cancers (Liu et al 2016). TRPM8 is involved in a variety of other cancers including adenocarcinoma, melanomas, as well as lung and breast cancers (Liu et al 2016). In 2002, two independent research groups identified TRPM8 as a cold (<28 °C) and menthol activated ion channel (McKemy et al 2002; Peier et al 2002).…”

“…In 2002, two independent research groups identified TRPM8 as a cold (<28 °C) and menthol activated ion channel (McKemy et al 2002; Peier et al 2002). Other chemical agonists for TRPM8 include cooling agents such as eucalyptol and icilin (Liu et al 2016). The temperature threshold of TRPM8 can be modulated by changes in membrane potential, arachidonic acid, lysophospholipids and PIP 2 (Liu et al 2016).…”

“…Other chemical agonists for TRPM8 include cooling agents such as eucalyptol and icilin (Liu et al 2016). The temperature threshold of TRPM8 can be modulated by changes in membrane potential, arachidonic acid, lysophospholipids and PIP 2 (Liu et al 2016). There is also evidence that G-proteins are involved in regulation of TRPM8, specifically, Gαq is involved in the inflammation mediated inhibition of TRPM8 (Liu et al 2016).…”