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142259 - Activation of the ion channel.pdf (3.02 MB)

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

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posted on 2023-05-20, 20:03 authored by Iman AzimiIman Azimi, Robitaille, M, Armitage, K, So, CL, Milevskiy, MJG, Northwood, K, Lim, HF, Thompson, EW, Roberts-Thomson, SJ, Monteith, GR
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.

History

Publication title

International Journal of Molecular Sciences

Volume

21

Issue

24

Article number

9417

Number

9417

Pagination

1-14

ISSN

1422-0067

Department/School

School of Pharmacy and Pharmacology

Publisher

Molecular Diversity Preservation International

Place of publication

Matthaeusstrasse 11, Basel, Switzerland, Ch-4057

Rights statement

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/).

Repository Status

  • Open

Socio-economic Objectives

Expanding knowledge in the biomedical and clinical sciences

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