Activation of the ion channel TRPV4 induces epithelial to mesenchymal transition in breast cancer cells
- Author(s)
- Azimi, I; Robitaille, M; Armitage, K; So, CL; Milevskiy, MJG; Northwood, K; Lim, HF; Thompson, EW; Roberts-Thomson, SJ; Monteith, GR;
- Details
- Publication Year 2020-12-10,Volume 21,Issue #24,Page 9417
- Journal Title
- Intermational Journal of Molecular Science
- Publication Type
- Journal Article
- 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.
- Publisher
- MDPI
- Keywords
- Emt; Trpv4; breast cancer; calcium channel
- Research Division(s)
- Cancer Biology And Stem Cells
- PubMed ID
- 33322037
- Publisher's Version
- https://doi.org/10.3390/ijms21249417
- Open Access at Publisher's Site
https://doi.org/10.3390/ijms21249417- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-02-01 12:08:28
Last Modified: 2021-03-03 08:55:20