54822

TRPM7

transient receptor potential cation channel, subfamily M, member 7;TRPM7;transient receptor potential cation channel, subfamily M, member 7

LTRPC ion channel family member 7|channel-kinase 1|long transient receptor potential channel 7|transient receptor potential cation channel subfamily M member 7|transient receptor potential-phospholipase C-interacting kinase

15q21

protein-coding

TRPM7 encodes a Ca2+-permeable nonselective cation channel with kinase activity. TRPM7 has been implicated in control of cell adhesion and migration, but whether TRPM7 activity contributes to cancer progression has not been established. Here we report that high levels of TRPM7 expression independently predict poor outcome in breast cancer patients and that it is functionally required for metastasis formation in a mouse xenograft model of human breast cancer. Mechanistic investigation revealed that TRPM7 regulated myosin II-based cellular tension, thereby modifying focal adhesion number, cell-cell adhesion and polarized cell movement. Our findings therefore suggest that TRPM7 is part of a mechanosensory complex adopted by cancer cells to drive metastasis formation.

metastasis is an inherent feature of breast cancer and transient receptor potential (TRP) channels were found to be potentially implicated in this process. Particularly, TRPM7 may regulate cell motility. We therefore examined the expression of TRPM7 mRNA in the Oncomine database and found that TRPM7 is correlated to metastasis and invasive breast cancer. Silencing TRPM7 with RNA interference resulted in a significant decrease in migration and invasion capability of MDA-MB-435 breast cancer cells, and phosphorylation levels of Src and MAPK but not AKT. Our results suggest that TRPM7 regulates migration and invasion of metastatic breast cancer cells via MAPK pathway.