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Activation of the Ion Channel TRPV4 Induces Epithelial to Mesenchymal Transition in Breast Cancer Cells

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...

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Autores principales: Azimi, Iman, Robitaille, Mélanie, Armitage, Kaela, So, Choon Leng, Milevskiy, Michael J. G., Northwood, Korinne, Lim, Huai Fang, Thompson, Erik W., Roberts-Thomson, Sarah J., Monteith, Gregory R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764818/
https://www.ncbi.nlm.nih.gov/pubmed/33322037
http://dx.doi.org/10.3390/ijms21249417
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author Azimi, Iman
Robitaille, Mélanie
Armitage, Kaela
So, Choon Leng
Milevskiy, Michael J. G.
Northwood, Korinne
Lim, Huai Fang
Thompson, Erik W.
Roberts-Thomson, Sarah J.
Monteith, Gregory R.
author_facet Azimi, Iman
Robitaille, Mélanie
Armitage, Kaela
So, Choon Leng
Milevskiy, Michael J. G.
Northwood, Korinne
Lim, Huai Fang
Thompson, Erik W.
Roberts-Thomson, Sarah J.
Monteith, Gregory R.
author_sort Azimi, Iman
collection PubMed
description 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.
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spelling pubmed-77648182020-12-27 Activation of the Ion Channel TRPV4 Induces Epithelial to Mesenchymal Transition in Breast Cancer Cells Azimi, Iman Robitaille, Mélanie Armitage, Kaela So, Choon Leng Milevskiy, Michael J. G. Northwood, Korinne Lim, Huai Fang Thompson, Erik W. Roberts-Thomson, Sarah J. Monteith, Gregory R. Int J Mol Sci Article 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. MDPI 2020-12-10 /pmc/articles/PMC7764818/ /pubmed/33322037 http://dx.doi.org/10.3390/ijms21249417 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Azimi, Iman
Robitaille, Mélanie
Armitage, Kaela
So, Choon Leng
Milevskiy, Michael J. G.
Northwood, Korinne
Lim, Huai Fang
Thompson, Erik W.
Roberts-Thomson, Sarah J.
Monteith, Gregory R.
Activation of the Ion Channel TRPV4 Induces Epithelial to Mesenchymal Transition in Breast Cancer Cells
title Activation of the Ion Channel TRPV4 Induces Epithelial to Mesenchymal Transition in Breast Cancer Cells
title_full Activation of the Ion Channel TRPV4 Induces Epithelial to Mesenchymal Transition in Breast Cancer Cells
title_fullStr Activation of the Ion Channel TRPV4 Induces Epithelial to Mesenchymal Transition in Breast Cancer Cells
title_full_unstemmed Activation of the Ion Channel TRPV4 Induces Epithelial to Mesenchymal Transition in Breast Cancer Cells
title_short Activation of the Ion Channel TRPV4 Induces Epithelial to Mesenchymal Transition in Breast Cancer Cells
title_sort activation of the ion channel trpv4 induces epithelial to mesenchymal transition in breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764818/
https://www.ncbi.nlm.nih.gov/pubmed/33322037
http://dx.doi.org/10.3390/ijms21249417
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