Cholesterol-induced activation of TRPM7 regulates cell proliferation, migration, and viability of human prostate cells.
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 Ca(2+) entry via the TRPM7 channel, which promoted proliferation of prostate cells by inducing the activation of the AKT and/or the ERK pathway. Additionally, cholesterol mediated Ca(2+) entry induced calpain activity that showed a decrease in E-cadherin expression, which together could lead to migration of prostate cancer cells. An overexpression of TRPM7 significantly facilitated cholesterol dependent Ca(2+) 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.
Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58201, USA.
Yuyang
Y
Sun
Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58201, USA.
Pramod
P
Sukumaran
Department of Internal Medicine, School of Medicine and Health Sciences, Fargo, ND 58102, USA.
Archana
A
Varma
Department of Internal Medicine, School of Medicine and Health Sciences, Fargo, ND 58102, USA.
Susan
S
Derry
Department of Internal Medicine, School of Medicine and Health Sciences, Fargo, ND 58102, USA.
Abe E
AE
Sahmoun
Department of Basic Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58201, USA. Electronic address: brij.singh@med.und.edu.
Brij B
BB
Singh
D000368:Aged; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000494:pharmacology*; D003710:Demography; D055786:Gene Knockout Techniques; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D008954:Models, Biological; D011467:Prostate / Q000378:metabolism* / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases; D050053:TRPM Cation Channels / Q000378:metabolism*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D050053:TRPM Cation Channels; D002784:Cholesterol; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; D002118:Calcium
Calcium and signal transduction; Cell proliferation and migration; Cholesterol; Prostate cancer; Statin; TRPM7