TRPM7 Ion Channel: Oncogenic Roles and Therapeutic Potential in Breast Cancer

Abstract

The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a divalent cations permeant channel but also has intrinsic serine/threonine kinase activity. It is ubiquitously expressed in normal tissues and studies have indicated that it participates in important physiological and pharmacological processes through its channel-kinase activity, such as calcium/magnesium homeostasis, phosphorylation of proteins involved in embryogenesis or the cellular process. Accumulating evidence has shown that TRPM7 is overexpressed in human pathologies including breast cancer. Breast cancer is the second leading cause of cancer death in women with an incidence rate increase of around 0.5% per year since 2004. The overexpression of TRPM7 may be associated with a poor prognosis in breast cancer patients, so more efforts are needed to research a new therapeutic target. TRPM7 regulates the levels of Ca2+, which can alter the signaling pathways involved in survival, cell cycle progression, proliferation, growth, migration, invasion, epithelial-mesenchymal transition and thus determines cell behavior, promoting tumor development. This work provides a complete overview of the TRPM7 ion channel and its main involvements in breast cancer. Special consideration is given to the modulation of the channel as a potential target in breast cancer treatment by inhibition of proliferation, migration and invasion. Taken together, these data suggest the potential exploitation of TRPM7 channel-kinase as a therapeutic target and a diagnostic biomarker.

Novel determinants of NOTCH1 trafficking and signaling in breast epithelial cells

“…Some of the identified genes that have previously been associated with Notch signaling appear connected with cation regulation, even if we identified the vast majority in unstimulated conditions ( CALM2, HCN2, MAP3K12, TRPM7 ). A case in point is that of TRPM7, encoding the transient receptor potential melastatin-related 7, a divalent Ca 2+ and Mg 2+ channel fused with a functional serine/threonine-protein kinase that is widely overexpressed in breast cancer (reviewed by [109]. Remarkably, TRPM7 has been described as a potent inducer of Notch activation during glial tumorigenesis [110, 111].…”

TRPM7 via calcineurin/NFAT pathway mediates metastasis and chemotherapeutic resistance in head and neck squamous cell carcinoma

“…Currently, the TRP family in vertebrates comprises eight subfamilies [ 6 , 7 ]. TRP channel dysfunction is associated with a spectrum of disorders [ 8 ]. However, the role of TRP channels as an anticancer drug target remains to be explored.…”

Promoter methylation of transient receptor potential melastatin-related 7 (TRPM7) predicts a better prognosis in patients with Luminal A breast cancers

“…For gastric cancer, several studies suggest that TRPM7 participates in the survival of human gastric adenocarcinoma cells by acting as detoxifiers [28][29][30].Also, there are studies suggesting that TRPM7 expression is significantly higher in invasive breast ductal carcinomas compared with control subjects, and demonstrating that TRPM7 is involve in regulating breast cancer cell proliferation, apoptosis, EMT, migration, invasion and microcalcification [31,32]. Given that approximately 15%-20% of breast cancer patients diagnosed with triple negative breast cancer (TNBC) in the United States and lack appropriate targeted therapeutic drugs, chemical modulators of the TRPM7 channel might potentially be used in therapeutic applications [33,34].…”