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Activation of the ion channel induces epithelial to mesenchymal transition in breast cancer cells

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Azimi, I ORCID: 0000-0001-9477-9999, Robitaille, M, Armitage, K, So, CL, Milevskiy, MJG, Northwood, K, Lim, HF, Thompson, EW, Roberts-Thomson, SJ and Monteith, GR 2020 , 'Activation of the ion channel induces epithelial to mesenchymal transition in breast cancer cells' , International Journal of Molecular Sciences, vol. 21, no. 24 , pp. 1-14 , doi: 10.3390/ijms21249417.

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Abstract

Epithelial to mesenchymal transition (EMT) in cancer is important in therapeutic resistance and invasiveness. Calcium signaling is key to the induction of EMT in breast cancer cells. Although inhibition of specific calcium-permeable ion channels regulates the induction of a sub-set of EMT markers in breast cancer cells, it is still unclear if activation of a specific calcium channel can be a driver for the induction of EMT events. In this study, we exploited the availability of a selective pharmacological activator of the calcium-permeable ion channel TRPV4 to assess the direct role of calcium influx in EMT marker induction. Gene association studies revealed a link between TRPV4 and gene-ontologies associated with EMT and poorer relapse-free survival in lymph node-positive basal breast cancers. TRPV4 was an important component of the calcium influx phase induced in MDA-MB-468 breast cancer cells by the EMT inducer epidermal growth factor (EGF). Pharmacological activation of TRPV4 then drove the induction of a variety of EMT markers in breast cancer cells. These studies demonstrate that calcium influx through specific pathways appears to be sufficient to trigger EMT events.

Item Type: Article
Authors/Creators:Azimi, I and Robitaille, M and Armitage, K and So, CL and Milevskiy, MJG and Northwood, K and Lim, HF and Thompson, EW and Roberts-Thomson, SJ and Monteith, GR
Keywords: Calcium, EMT, cancer, TRPV4, pharmacological modulation, calcium channel, breast cancer
Journal or Publication Title: International Journal of Molecular Sciences
Publisher: Molecular Diversity Preservation International
ISSN: 1422-0067
DOI / ID Number: 10.3390/ijms21249417
Copyright Information:

Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons 4.0 International (CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/).

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