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The Role of Transient Receptor Potential Melastatin 7 (TRPM7) in Cell Viability: A Potential Target to Suppress
Hengrui Liu1, James P Dilger1, Jun Lin1
1Department of Anesthesiology, Health Science Center, Stony Brook University, Stony Brook, NY 11794, USA.
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.
Insights
Transient Receptor Potential Melastatin 7 (TRPM7) inhibitors suppressed breast cancer cell viability by disrupting the cell cycle. TRPM7 is a potential therapeutic target for breast cancer treatment.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- The role of the divalent cation-selective channel Transient Receptor Potential Melastatin 7 (TRPM7) in breast cancer viability is not well understood.
- Previous studies suggest TRPM7 influences the proliferation of various cancer cells.
Purpose of the Study:
- To investigate the function of TRPM7 in breast cancer cell viability.
- To determine if TRPM7 is a viable therapeutic target for breast cancer.
Main Methods:
- Utilized TRPM7 inhibitors (2-aminoethyl diphenylborinate, ginsenoside Rd, waixenicin A) on TRPM7-expressing and wildtype HEK293 cells.
- Assessed TRPM7 channel function via whole-cell currents and divalent cation influx.
- Examined the effect of TRPM7 inhibition on breast cancer cell lines (MDA-MB-231, AU565, T47D) and a TRPM7 knock-out cell line (KO-231).
- Analyzed cell cycle progression and cell death.
Main Results:
- TRPM7 inhibitors preferentially suppressed the viability of TRPM7-overexpressing cells compared to wildtype cells.
- 2-aminoethyl diphenylborinate inhibited TRPM7 channel function and breast cancer cell viability by arresting the cell cycle at the S phase, not by inducing cell death.
- TRPM7 knock-out cells exhibited reduced divalent cation influx and proliferation.
- TRPM7 inhibitors demonstrated preferential suppression of wildtype breast cancer cells over knock-out cells, targeting the cell cycle.
Conclusions:
- TRPM7 plays a significant role in regulating the cell cycle of breast cancer cells.
- TRPM7 is a promising therapeutic target for breast cancer treatment.
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