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Oncosis and apoptosis induction by activation of an overexpressed ion channel in breast cancer cells

Citation

Peters, AA and Jamaludin, SYN and Yapa, KTDS and Chalmers, S and Wiegmans, AP and Lim, HF and Milevskiy, MJG and Azimi, I and Davis, FM and Northwood, KS and Pera, E and Marcial, DL and Dray, E and Waterhouse, NJ and Cabot, PJ and Gonda, TJ and Kenny, PA and Brown, MA and Khanna, KK and Roberts-Thomson, SJ and Monteith, GR, Oncosis and apoptosis induction by activation of an overexpressed ion channel in breast cancer cells, Oncogene, 36, (46) pp. 6490-6500. ISSN 0950-9232 (2017) [Refereed Article]

DOI: doi:10.1038/onc.2017.234

Abstract

The critical role of calcium signalling in processes related to cancer cell proliferation and invasion has seen a focus on pharmacological inhibition of overexpressed ion channels in specific cancer subtypes as a potential therapeutic approach. However, despite the critical role of calcium in cell death pathways, pharmacological activation of overexpressed ion channels has not been extensively evaluated in breast cancer. Here we define the overexpression of transient receptor potential vanilloid 4 (TRPV4) in a subgroup of breast cancers of the basal molecular subtype. We also report that pharmacological activation of TRPV4 with GSK1016790A reduced viability of two basal breast cancer cell lines with pronounced endogenous overexpression of TRPV4, MDA-MB-468 and HCC1569. Pharmacological activation of TRPV4 produced pronounced cell death through two mechanisms: apoptosis and oncosis in MDA-MB-468 cells. Apoptosis was associated with PARP-1 cleavage and oncosis was associated with a rapid decline in intracellular ATP levels, which was a consequence of, rather than the cause of, the intracellular ion increase. TRPV4 activation also resulted in reduced tumour growth in vivo. These studies define a novel therapeutic strategy for breast cancers that overexpress specific calcium permeable plasmalemmal ion channels with available selective pharmacological activators.

Item Details

Item Type:Refereed Article
Keywords:Oncosis and apoptosis induction by activation of an overexpressed ion channel in breast cancer cells
Research Division:Biomedical and Clinical Sciences
Research Group:Oncology and carcinogenesis
Research Field:Cancer cell biology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Azimi, I (Dr Iman Azimi)
ID Code:124405
Year Published:2017
Web of Science® Times Cited:38
Deposited By:Pharmacy
Deposited On:2018-02-21
Last Modified:2018-03-15
Downloads:0

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