The Role of Transient Receptor Potential Melastatin 7 (TRPM7) in Cell Viability: A Potential Target to Suppress Breast Cancer Cell Cycle

Abstract

The divalent cation-selective channel transient receptor potential melastatin 7 (TRPM7) channel was shown to affect the proliferation of some types of cancer cell. However, the function of TRPM7 in the viability of breast cancer cells remains unclear. Here we show that TRPM inhibitors suppressed the viability of TRPM7-expressing breast cancer cells. We first demonstrated that the TRPM7 inhibitors 2-aminoethyl diphenylborinate (2-APB), ginsenoside Rd (Gin Rd), and waixenicin A preferentially suppressed the viability of human embryonic kidney HEK293 overexpressing TRPM7 (HEK-M7) cells over wildtype HEK293 (WT-HEK). Next, we confirmed the effects of 2-APB on the TRPM7 channel functions by whole-cell currents and divalent cation influx. The inhibition of the viability of HEK-M7 cells by 2-APB was not mediated by the increase in cell death but by the interruption of the cell cycle. Similar to HEK-M7 cells, the viability of TRPM7-expressing human breast cancer MDA-MB-231, AU565, and T47D cells were also suppressed by 2-APB by arresting the cell cycle in the S phase. Furthermore, in a novel TRPM7 knock-out MDA-MB-231 (KO-231) cell line, decreased divalent influx and reduced proliferation were observed compared to the wildtype MDA-MB-231 cells. 2-APB and Gin Rd preferentially suppressed the viability of wildtype MDA-MB-231 cells over KO-231 by affecting the cell cycle in wildtype but not KO-231 cells. Our results suggest that TRPM7 regulates the cell cycle of breast cancers and is a potential therapeutic target.

Knockdown of TRPM7 prevents tumor growth, migration, and invasion through the Src, Akt, and JNK pathway in bladder cancer

“…Recently, TRPM7 has been reported to be implicated in carcinogenesis and has been considered as a potential target for diverse cancer treatment [27,31]. TRPM7, one of the TRP member channels, is permeable to Ca 2+ and Mg 2+ .…”

“…TRPM7, one of the TRP member channels, is permeable to Ca 2+ and Mg 2+ . Since Ca 2+ is an important regulator of cell cycle and proliferation, TRPM7 regulation is considered to be critical to the biological function of cancer cells [31]. TRPM7 is reported to be overexpressed in human pulmonary adenocarcinoma, and pancreatic and prostate adenocarcinoma [18,32].…”

A novel TRPM7/O-GlcNAc axis mediates tumour cell motility and metastasis by stabilising c-Myc and caveolin-1 in lung carcinoma

“…To study the dose–response pattern of TRPM7 inhibition, pharmacological inhibition of TRPM7 was performed in conjunction with CRISPR/Cas9-mediated genetic manipulation of TRPM7 using 2-aminoethyl diphenylborinate (2-APB). 2-APB is a general TRP channel blocker that has been shown to inhibit TRPM7 currents in a dose-dependent manner, 25 – 27 although this inhibitor is not only specific to TRPM7.…”

A bibliometric analysis and review of recent researches on TRPM7

“…Moreover, the TRPM7 channel serves as a regulator of epithelial-mesenchymal transition (EMT) by meditating signal transducer, and as an activator of transcription 3 (STAT3) phosphorylation as well as vimentin expression. Inhibiting TRPM7 in breast cancer cell lines with 2-APB caused an increment in the percentage of cells in the S phase and a decreased cell population in the G0/G1 phase [49]. In prostate cancer, scientists reported that TRPM7 mediated-Mg 2+ influx promoted the cell migration by inducing EMT, and TRPM7 suppression alleviated TGFβ-induced cell migration with a reduction of EMT markers [50].…”