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Cancers 2018, 10(9), 331; https://doi.org/10.3390/cancers10090331

TRPC6 Channels Are Required for Proliferation, Migration and Invasion of Breast Cancer Cell Lines by Modulation of Orai1 and Orai3 Surface Exposure

1
Cellular Physiology Research Group, Department of Physiology, Institute of Molecular Pathology Biomarkers, University of Extremadura, 10003 Caceres, Spain
2
Department of Medical Physiology and Biophysic, Institute of Biomedicine of Sevilla, 41013 Sevilla, Spain
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 5 August 2018 / Revised: 7 September 2018 / Accepted: 13 September 2018 / Published: 14 September 2018
(This article belongs to the Special Issue Ion Channels in Cancer)
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Abstract

Transient receptor potential channels convey signaling information from a number of stimuli to a wide variety of cellular functions, mainly by inducing changes in cytosolic Ca2+ concentration. Different members of the TRPC, TRPM and TRPV subfamilies have been reported to play a role in tumorigenesis. Here we show that the estrogen receptor positive and triple negative breast cancer cell lines, MCF7 and MDA-MB-231, respectively, exhibit enhanced expression of the TRPC6 channel as compared to the non-tumoral MCF10A cell line. In vitro TRPC6 knockdown using shRNA impaired MCF7 and MDA-MB-231 cell proliferation, migration and invasion detected by BrdU incorporation, wound healing and Boyden chamber assays, respectively. Using RNAi-mediated TRPC6 silencing as well as overexpression of the pore-dead dominant-negative TRPC6 mutant we have found that TRPC6 plays a relevant role in the activation of store-operated Ca2+ entry in the breast cancer cell lines but not in non-tumoral breast cells. Finally, we have found that TRPC6 interacts with Orai1 and Orai3 in MCF7 and MDA-MB-231 cells and is required for the translocation of Orai1 and Orai3 to the plasma membrane in MDA-MB-231 and MCF7 cells, respectively, upon Ca2+ store depletion. These findings introduce a novel mechanism for the modulation of Ca2+ influx and the development of different cancer hallmarks in breast cancer cells. View Full-Text
Keywords: TRPC6; Orai1; Orai3; store-operated calcium entry; MCF7; MDA-MB-231 TRPC6; Orai1; Orai3; store-operated calcium entry; MCF7; MDA-MB-231
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Jardin, I.; Diez-Bello, R.; Lopez, J.J.; Redondo, P.C.; Salido, G.M.; Smani, T.; Rosado, J.A. TRPC6 Channels Are Required for Proliferation, Migration and Invasion of Breast Cancer Cell Lines by Modulation of Orai1 and Orai3 Surface Exposure. Cancers 2018, 10, 331.

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