Differential effects of two-pore channel protein 1 and 2 silencing in MDA-MB-468 breast cancer cells

Biochem Biophys Res Commun. 2016 Sep 2;477(4):731-736. doi: 10.1016/j.bbrc.2016.06.127. Epub 2016 Jun 25.

Abstract

Two-pore channel proteins, TPC1 and TPC2, are calcium permeable ion channels found localized to the membranes of endolysosomal calcium stores. There is increasing interest in the role of TPC-mediated intracellular signaling in various pathologies; however their role in breast cancer has not been extensively evaluated. TPC1 and TPC2 mRNA was present in all non-tumorigenic and tumorigenic breast cell lines assessed. Silencing of TPC2 but not TPC1 attenuated epidermal growth factor-induced vimentin expression in MDA-MB-468 breast cancer cells. This effect was not due to a general inhibition of epithelial to mesenchymal transition (EMT) as TPC2 silencing had no effect on epidermal growth factor (EGF)-induced changes on E-cadherin expression. TPC1 and TPC2 were also shown to differentially regulate cyclopiazonic acid (CPA)-mediated changes in cytosolic free Ca(2+). These findings indicate potential differential regulation of signaling processes by TPC1 and TPC2 in breast cancer cells.

Keywords: Breast cancer; Calcium; Calcium signaling; Epidermal growth factor; Two-pore channel; Vimentin.

MeSH terms

  • Breast Neoplasms / metabolism*
  • Calcium / metabolism
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Calcium Signaling*
  • Cell Line, Tumor
  • ErbB Receptors / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Humans
  • Ion Channel Gating
  • Vimentin / metabolism*

Substances

  • Calcium Channels
  • TPCN1 protein, human
  • TPCN2 protein, human
  • Vimentin
  • EGFR protein, human
  • ErbB Receptors
  • Calcium