Increase in serum Ca2+/Mg2+ ratio promotes proliferation of prostate cancer cells by activating TRPM7 channels

Yuyang Sun, Senthil Selvaraj, Archana Varma, Susan Derry, Abe E. Sahmoun, Brij B. Singh

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

TRPM7 is a novel magnesium-nucleotide-regulated metal current (MagNuM) channel that is regulated by serum Mg2+ concentrations. Changes in Mg2+ concentration have been shown to alter cell proliferation in various cells; however, the mechanism and the ion channel(s) involved have not yet been identified. Here we demonstrate that TRPM7 is expressed in control and prostate cancer cells. Supplementation of intracellular Mg-ATP or addition of external 2-aminoethoxydiphenyl borate inhibited MagNuM currents. Furthermore, silencing of TRPM7 inhibited whereas overexpression of TRPM7 increased endogenous MagNuM currents, suggesting that these currents are dependent on TRPM7. Importantly, although an increase in the serum Ca2+/Mg 2+ ratio facilitated Ca2+ influx in both control and prostate cancer cells, a significantly higher Ca2+ influx was observed in prostate cancer cells. TRPM7 expression was also increased in cancer cells, but its expression was not dependent on the Ca2+/Mg 2+ ratio per se. Additionally, an increase in the extracellular Ca2+/Mg2+ ratio led to a significant increase in cell proliferation of prostate cancer cells when compared with control cells. Consistent with these results, age-matched prostate cancer patients also showed a subsequent increase in the Ca2+/Mg2+ ratio and TRPM7 expression. Altogether, we provide evidence that the TRPM7 channel has an important role in prostate cancer and have identified that the Ca 2+/Mg2+ ratio could be essential for the initiation/progression of prostate cancer.

Original languageEnglish
Pages (from-to)255-263
Number of pages9
JournalJournal of Biological Chemistry
Volume288
Issue number1
DOIs
Publication statusPublished - 4 Jan 2013
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

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