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

Yuyang Sun, Pramod Sukumaran, Archana Varma, Susan Derry, Abe E. Sahmoun, Brij B. Singh

Research output: Contribution to journalArticle

46 Scopus citations

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 the 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. An 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.

Original languageEnglish (US)
Pages (from-to)1839-1850
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1843
Issue number9
DOIs
StatePublished - Sep 2014

    Fingerprint

Keywords

  • Calcium and signal transduction
  • Cell proliferation and migration
  • Cholesterol
  • Prostate cancer
  • Statin
  • TRPM7

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this