期刊
CANCERS
卷 10, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/cancers10090331
关键词
TRPC6; Orai1; Orai3; store-operated calcium entry; MCF7; MDA-MB-231
类别
资金
- MINECO [BFU2016-74932-C2-1-P, BFU2013-45564-C2, BFU2016-74932-C2]
- Junta de Extremadura-FEDER (Fondo Europeo de Desarrollo Regional Grants) [IB16046, GR15029, GR18061]
- Junta de Extremadura [IB16046]
- Juan de la Cierva (Ministry of Industry, Economy and Competitiveness, Spain) [IJCI-2015-25665]
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.
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