The oncogenic roles of TRPM ion channels in cancer

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.

Evaluation of the TRPM protein family as potential biomarkers for various types of human cancer using public database analyses

“…The results suggested that certain members of the TRPM family may be potential biomarkers and targets for new breast cancer therapies. Associations between TRPM proteins and breast cancer continue to be identified as a result of rapid advances in molecular biology and genetics research ( 9 ). In addition, TRPM6 somatic mutations have also been observed in an independent cohort of breast cancer samples ( 64 ).…”

“…TRPM7 has been considered to regulate the migration and invasion of metastatic breast cancer cells ( 7 ). Taken together, the TRPM protein family may be attractive targets for anticancer therapies or prognostic biomarkers in certain types of human cancer ( 8 , 9 ). However, to the best of our knowledge, a systematic study on the transcriptional expression and prognostic value of the TRPM protein family members in human tumors has not been conducted yet.…”

Identification of the role of TRPM8 in glioblastoma and its effect on proliferation, apoptosis and invasion of the U251 human glioblastoma cell line

“…As the subclass of the TRP channels, TRPMs have varying permeability to Ca 2+ and Mg 2+ in various types of cancer (5,26,27). Therefore, TRPM protein family members may serve attractive targets for anticancer therapeutic strategies or prognostic biomarkers to cure specific types of cancers (26,28). It is common knowledge that TRPM8 is involved in the initiation and progression of tumors (29,30).…”

“…Although these findings undoubtledly require scrutinization, they suggested that TRPM8 may be involved in the transformation of normal cells to tumorigenic cells, which culminates in biological changes, such as tumor proliferation, apoptosis, gene transcription and angiogenesis (31). Morever, few studies have been performed where the gene expression data is correlated with the survival of patients (8,9,11,28). Combined, TRPM8 may serve as an appropriate GBM biomarker, and this biomarker is urgently required for the early diagnosis and validation of interventions.…”

A bibliometric analysis and review of recent researches on TRPM7

“…They function as gatekeepers by mediating ion fluxes in response to various sensory stimulus including temperature, vision, taste, and pain [1]. In mammals, the TRP superfamily includes 28 members, which can be subdivided into 6 subfamilies: TRPA (ankyrin), TRPC (canonical), TRPM (melastatin), TRPML (mucolipin), TRPP (polycystin), and TRPV, but humans only express 27 TRP channel members [2,3]. There are eight members in the TRPM subfamily (TRPM1-8), and each member consists of six transmembrane domains with a pore-forming loop, and the N-and C-termini directed to the cytoplasm.…”