Cholesterol-induced activation of TRPM7 regulates cell proliferation, migration, and viability of human prostate cells.
Cholesterol-induced activation of TRPM7 regulates cell proliferation, migration, and viability of human prostate cells.
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DOI：
10.1016/j.bbamcr.2014.04.019
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发表时间：
2014-09
影响因子：
5.1
通讯作者：
Singh, Brij B.
中科院分区：
文献类型：
--
作者：
Sun, Yuyang;Sukumaran, Pramod;Varma, Archana;Derry, Susan;Sahmoun, Abe E.;Singh, Brij B.
关键词：
胆固醇已被证明可促进许多细胞的细胞增殖/迁移;然而，其机制尚未完全确定。在这里，我们证明，胆固醇增加Ca 2+通过TRPM 7通道，这促进了前列腺细胞的增殖，通过诱导AKT和/或ERK通路的激活。此外，胆固醇介导的Ca 2+内流诱导钙蛋白酶活性，其显示E-钙粘蛋白表达的降低，其一起可导致前列腺癌细胞的迁移。TRPM 7的过表达显著促进胆固醇依赖性Ca 2+内流、细胞增殖和肿瘤生长。然而，TRPM 7沉默或他汀类药物抑制胆固醇合成显示胆固醇介导的TRPM 7活化、细胞增殖和前列腺癌细胞迁移显著降低。与这些结果一致，他汀类药物摄入与前列腺癌患者呈负相关，并且在从前列腺癌患者获得的样品中观察到TRPM 7表达的增加。总之，我们提供了证据表明胆固醇介导的TRPM 7活化对前列腺癌很重要，并且已经确定TRPM 7可能是前列腺癌的起始和/或进展所必需的。
Cholesterol has been shown to promote cell proliferation/migration in many cells; however the mechanism(s) have not yet been fully identified. Here we demonstrate that cholesterol increases Ca2+ entry via the TRPM7 channel, which promoted proliferation of prostate cells by inducing activation of the AKT and/or the ERK pathway. Additionally, cholesterol mediated Ca2+ entry induced calpain activity that showed a decrease in E-cadherin expression, which together could lead to migration of prostate cancer cells. Overexpression of TRPM7 significantly facilitated cholesterol dependent Ca2+ entry, cell proliferation and tumor growth. Whereas, TRPM7 silencing or inhibition of cholesterol synthesis by statin showed a significant decrease in cholesterol-mediated activation of TRPM7, cell proliferation, and migration of prostate cancer cells. Consistent with these results, statin intake was inversely correlated with prostate cancer patients and increase in TRPM7 expression was observed in samples obtained from prostate cancer patients. Altogether, we provide evidence that cholesterol-mediated activation of TRPM7 is important for prostate cancer and have identified that TRPM7 could be essential for initiation and/or progression of prostate cancer.
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