In breast cancer cells, however, Orai1 gating is independent on Stim1 and is not driven by ER Ca2+ store depletion; accordingly, Orai1 is activated by the Secretory Pathway Ca2+-ATPase, SPCA2, in MCF-7 cells [17] and by a yet to be identified mechanism in MDA-MB-435 cells [18]. This evidence concerns the gene ATP2C2 and breast cancer.