The Role of Transient Receptor Potential Melastatin 7 (TRPM7) in Cell Viability: A Potential Target to Suppress Breast Cancer Cell Cycle
The Role of Transient Receptor Potential Melastatin 7 (TRPM7) in Cell Viability: A Potential Target to Suppress Breast Cancer Cell Cycle
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DOI：
10.3390/cancers12010131
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发表时间：
2020-01-01
期刊：
影响因子：
5.2
通讯作者：
Lin, Jun
中科院分区：
文献类型：
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作者：
Liu, Hengrui;Dilger, James P.;Lin, Jun
二价阳离子选择通道瞬时受体电位美拉他汀7 （TRPM7）通道可影响某些类型癌细胞的增殖。然而，TRPM7在乳腺癌细胞存活中的功能尚不清楚。本研究表明，TRPM抑制剂抑制了表达trpm7的乳腺癌细胞的活力。我们首先证明TRPM7抑制剂2-氨基乙基二苯硼酸盐（2-APB）、人参皂苷Rd （Gin Rd）和waixenicin A比野生型HEK293 （WT-HEK）优先抑制过表达TRPM7 （HEK-M7）的人胚胎肾HEK293细胞的活力。接下来，我们通过全细胞电流和二价阳离子内流证实了2-APB对TRPM7通道功能的影响。2-APB对HEK-M7细胞活力的抑制不是通过细胞死亡增加介导的，而是通过细胞周期的中断介导的。与HEK-M7细胞类似，表达trpm7的人乳腺癌MDA-MB-231、AU565和T47D细胞的活力也被2-APB抑制，通过将细胞周期阻滞在S期。此外，在一种新型TRPM7敲除MDA-MB-231 （KO-231）细胞系中，与野生型MDA-MB-231细胞相比，观察到二价内流减少和增殖减少。2-APB和Gin Rd通过影响野生型MDA-MB-231细胞的细胞周期而不影响KO-231细胞，从而优先抑制野生型MDA-MB-231细胞的活力。我们的研究结果表明，TRPM7调节乳腺癌的细胞周期，是一个潜在的治疗靶点。
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.