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

Aisyah H. Jahidin, Teneale A. Stewart, Erik W. Thompson, Sarah J. Roberts-Thomson, Gregory R. Monteith

Research output: Contribution to journalArticle

10 Scopus citations

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 Ca2+. These findings indicate potential differential regulation of signaling processes by TPC1 and TPC2 in breast cancer cells.

Original languageEnglish (US)
Pages (from-to)731-736
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume477
Issue number4
DOIs
StatePublished - Sep 2 2016

Keywords

  • Breast cancer
  • Calcium
  • Calcium signaling
  • Epidermal growth factor
  • Two-pore channel
  • Vimentin

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