Abstract
Transient receptor potential (TRP) proteins are a diverse family of ion channels present in multiple types of tissues. They function as gatekeepers for responses to sensory stimuli including temperature, vision, taste, and pain through their activities in conducting ion fluxes. The TRPM (melastatin) subfamily consists of eight members (i.e., TRPM1-8), which collectively regulate fluxes of various types of cations such as K+ , Na+ , Ca2+ , and Mg2+ . Growing evidence in the past two decades indicates that TRPM ion channels, their isoforms, or long noncoding RNAs encoded within the locus may be oncogenes involved in the regulation of cancer cell growth, proliferation, autophagy, invasion, and epithelial-mesenchymal transition, and their significant association with poor clinical outcomes of cancer patients. In this review, we describe and discuss recent findings implicating TRPM channels in different malignancies, their functions, mechanisms, and signaling pathways involved in cancers, as well as summarizing their normal physiological functions and the availability of ion channel pharmacological inhibitors.
Highlights
Ion channels are specialized membrane proteins that mediate ion fluxes
Accumulating evidence indicates that TRPM channels could serve as promising targets for cancer therapy
TRPM8 isoforms (Figure 2 and Figure 3) represent promising therapeutic targets in human malignancies where multiple lines of evidence have reported their overexpression in cancers and functional proof of their requirement for cancer cell growth, survival, invasion and/or epithelial-mesenchymal transition (EMT)
Summary
Ion channels are specialized membrane proteins that mediate ion fluxes. Their roles in shaping rapid signals in excitable cells such as neurons and cardiac myocytes have been widely known and traditionally studied by physiologists and biophysicists. Pioneering studies in the 1990s demonstrating the oncogenic properties of K+ channels sparked interest in examining the potential to target ion channels in malignancies (Arcangeli et al, 1993; Pardo et al, 1999). These proteins have since been subject to intensive investigations, and ion channels were found to be involved in processes crucial for non-excitable and cancer cells including maintaining cell viability, proliferation, cell adhesion and migration (Leanza, Manago, Zoratti, Gulbins, & Szabo, 2016).
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