Cholesterol-induced activation of TRPM7 regulates cell proliferation, migration, and viability of human prostate cells

Abstract

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.

Plasma membrane calcium channels in cancer: Alterations and consequences for cell proliferation and migration

“…This not only enhances TRPM7 expression, but also promotes cell proliferation in PCa cells [41]. Cholesterol increases Ca 2+ entry via the TRPM7 channel, which promotes the proliferation of prostate cells by inducing the activation of the AKT and/or the ERK pathways [41]. This may be one of the cellular mechanisms explaining why high circulating cholesterol levels have been shown to increase the risk of overall aggressive PCa [42].…”

“…TRPM7 is expressed in control and prostate cancer cells. It is of interest that an increase in the extracellular Ca 2+ /Mg 2+ ratio led to a significant increase in the cell proliferation of PCa cells when compared with control cells [41]. TRPM7 expression was not dependent on the Ca 2+ / Mg 2+ ratio per se.…”

“…However, the same group showed that cholesterol treatment activates TRPM7 channels, thereby increasing cytosolic Ca 2+ levels. This not only enhances TRPM7 expression, but also promotes cell proliferation in PCa cells [41]. Cholesterol increases Ca 2+ entry via the TRPM7 channel, which promotes the proliferation of prostate cells by inducing the activation of the AKT and/or the ERK pathways [41].…”

LXR agonist treatment of blastic plasmacytoid dendritic cell neoplasm restores cholesterol efflux and triggers apoptosis

“…9 These latter functions are implicated in survival signaling pathway activation (eg, Akt) 10 and proliferation. 11,12 For instance, stimulation of cholesterol efflux inhibits interleukin-3 (IL-3)-induced hematological progenitor cell proliferation. 13,14 Interestingly, BPDCN cells express high levels of IL-3 receptor a chain (CD123), and IL-3 is a BPDCN survival factor.…”

Transient Receptor Potential Melastatin 7 as an Independent Prognostic Factor in Human Esophageal Squamous Cell Carcinoma

“…Transient receptor potential malastatin 7 (TRPM7) is composed of a permeable Ca 2+ -Mg 2+ ion channel and an inherent serine/threonine kinase (2) and regulates many cellular processes including survival (3,4), proliferation (5-10), migration (8)(9)(10)(11)(12)(13)(14) and invasion (8). TRPM7 plays an important role in the proliferation of head and neck tumor cells (7), glioma cells (8), prostate cancer cells (9) and bladder cancer cells (10). Furthermore, TRPM7 regulates the migration of human nasopharyngeal carcinoma cells (12), breast cancer cells (13) and human pancreatic ductal adenocarcinoma cells (14).…”