Figure 1.

Function and regulation of SPCA2 in normal physiological conditions and cancerous cells. In normal physiological conditions, enhanced Ca²⁺ entry induced by upregulation of SPCA2 and its interaction with Orai1 is balanced by increased expression of Ca²⁺ pumps and buffering proteins mediating Ca²⁺ OUT. When transcellular Ca²⁺ is augmented, cytosolic Ca²⁺ is maintained at a low level. While in cancer cells, this orchestration is disrupted. Inhibited Ca²⁺ OUT synergizes with upregulated Ca²⁺ IN elicited by SPCA2–Orai1 to yield sustained elevation of cytosolic Ca²⁺ and thus constitutive activation of downstream signaling events controlling cell growth and survival which promote cell proliferation and tumorigenesis. SPCA, secretory pathway calcium ATPase.