New insights into store-independent Ca2+ entry: secretory pathway calcium ATPase 2 in normal physiology and cancer

摘要

Recent studies in secretory pathway calcium ATPases (SPCA) revealed novel functions of SPCA2 in interacting with store-operated Ca²⁺ channel Orai1 and inducing Ca²⁺ influx at the cell surface. Importantly, SPCA2-mediated Ca²⁺ signaling is uncoupled from its conventional role of Ca²⁺-ATPase and independent of store-operated Ca²⁺ signaling pathway. SPCA2-induced store-independent Ca²⁺ entry (SICE) plays essential roles in many important physiological processes, while unbalanced SICE leads to enhanced cell proliferation and tumorigenesis. Finally, we have summarized the clinical implication of SICE in oral cancer prognosis and treatment. Inhibition of SICE may be a new target for the development of cancer therapeutics.