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

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-13-induced EMT are still unclear. In this study, we demonstrate roles of STIMs in TGF-beta-induced EMT in breast cancer cells. In particular, STIM1 and STIM2 expression affected TGF-beta-induced EMT by mediating SOCE in MDAMB-231 and MCF-7 breast cancer cells. The specific SOCE inhibitor YM58483 blocked TGF-beta-induced EMT, and differing effects of STIM1 and STIM2 on TGF-beta-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-f3-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-beta-induced EMT and these effects are related to both SOCE and non-SOCE. (C) 2017 Elsevier Inc. All rights reserved.