Epithelial-mesenchymal transition (EMT), a process implicated in cancer metastasis, is associated with the transcriptional regulation of members of the ATP-binding cassette superfamily of efflux pumps, and drug resistance in breast cancer cells. Epidermal growth factor (EGF)-induced EMT in MDA-MB-468 breast cancer cells is calcium signal dependent. In this study induction of EMT was shown to result in the transcriptional up-regulation of ATP-binding cassette, subfamily C, member 3 (ABCC3), a member of the ABC transporter superfamily, which has a recognized role in multidrug resistance. Buffering of cytosolic free calcium inhibited EGF-mediated ABCC3 increases, indicating a calcium-dependent mode of regulation. Silencing of TRPM7 (an ion channel involved in EMT associated vimentin induction) did not inhibit ABCC3 up-regulation. Silencing of the store operated calcium entry (SOCE) pathway components ORAI1 and STIM1 also did not alter ABCC3 induction by EGF. However, the calcium permeable ion channel transient receptor potential cation channel, subfamily C, member 1 (TRPC1) appears to contribute to the regulation of both basal and EGF-induced ABCC3 mRNA. Improved understanding of the relationship between calcium signaling, EMT and the regulation of genes important in therapeutic resistance may help identify novel therapeutic targets for breast cancer.
|Original language||English (US)|
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Mar 13 2015|
Bibliographical noteFunding Information:
This research was partially supported by the Australian Government National Health and Medical Research Council (NHMRC) (project grant 1022263 ), and the Queensland Cancer Council (project grant 1042819 ). EWT was funded in part by the EMPathy Breast Cancer Program of the National Breast Cancer Foundation , Australia (project grant CG-10-04 ). TAS was funded by an NHMRC Dora Lush Biomedical Research Postgraduate Scholarship ( 1039358 ).
© 2015 Elsevier Inc. All rights reserved.
- Breast cancer
- Calcium signaling
- Epidermal growth factor
- Epithelial-mesenchymal transition