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

• Main Authors: Jahidin, AH (Author), Monteith, GR (Author), Roberts-Thomson, SJ (Author), Stewart, TA (Author), Thompson, EW (Author)
• Format: Article
• Language: English
• Published: 2016
• Subjects: ACTIVATION; Breast cancer; CA2+; Calcium; CALCIUM; Calcium signaling; ENTRY; Epidermal growth factor; EPITHELIAL-MESENCHYMAL TRANSITION; GENE-EXPRESSION; KINASES; LINES; NAADP; Two-pore channel; Vimentin
• Online Access: View Fulltext in Publisher
• DOI: 10.1016/j.bbrc.2016.06.127

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. (C) 2016 Elsevier Inc. All rights reserved.