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Activation of the ion channel induces epithelial to mesenchymal transition in breast cancer cells
Citation
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, Activation of the ion channel induces epithelial to mesenchymal transition in breast cancer cells, International Journal of Molecular Sciences, 21, (24) Article 9417. ISSN 1422-0067 (2020) [Refereed Article]
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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 Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | Calcium, EMT, cancer, TRPV4, pharmacological modulation, calcium channel, breast cancer |
| Research Division: | Biomedical and Clinical Sciences |
| Research Group: | Pharmacology and pharmaceutical sciences |
| Research Field: | Basic pharmacology |
| Objective Division: | Expanding Knowledge |
| Objective Group: | Expanding knowledge |
| Objective Field: | Expanding knowledge in the biomedical and clinical sciences |
| UTAS Author: | Azimi, I (Dr Iman Azimi) |
| ID Code: | 142259 |
| Year Published: | 2020 |
| Deposited By: | Pharmacy |
| Deposited On: | 2021-01-04 |
| Last Modified: | 2021-01-06 |
| Downloads: | 0 |
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