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

Abstract

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. © 2013 WCSS. All rights reserved.