STIM1 and STIM2 differently regulate endogenous Ca2+ entry and promote TGF-ß-induced EMT in breast cancer cells.

ABSTRACT

The Ca2+ sensor proteins STIM1 and STIM2 are crucial elements of store-operated calcium entry (SOCE) in breast cancer cells. Increased SOCE activity may contribute to epithelial-mesenchymal transitions (EMT) and increase cell migration and invasion. However, the roles of STIM1 and STIM2 in TGF-ß-induced EMT are still unclear. In this study, we demonstrate roles of STIMs in TGF-ß-induced EMT in breast cancer cells. In particular, STIM1 and STIM2 expression affected TGF-ß-induced EMT by mediating SOCE in MDA-MB-231 and MCF-7 breast cancer cells. The specific SOCE inhibitor YM58483 blocked TGF-ß-induced EMT, and differing effects of STIM1 and STIM2 on TGF-ß-induced EMT correlated with differing roles in SOCE. Finally, we showed that STIM2 is associated with non-store-operated calcium entry (non-SOCE) during TGF-ß-induced EMT, whereas STIM1 is not. What's more, non-SOCE have a large possibility to be ROCE. In conclusion, STIM1 and STIM2 proteins play important roles in TGF-ß-induced EMT and these effects are related to both SOCE and non-SOCE.