Lessons from the Endoplasmic Reticulum Ca²⁺ Transporters-A Cancer Connection

Ca²⁺ is an integral mediator of intracellular signaling, impacting almost every aspect of cellular life. The Ca²⁺-conducting transporters located on the endoplasmic reticulum (ER) membrane shoulder the responsibility of constructing the global Ca²⁺ signaling landscape. These transporters gate the ER Ca²⁺ release and uptake, sculpt signaling duration and intensity, and compose the Ca²⁺ signaling rhythm to accommodate a plethora of biological activities. In this review, we explore the mechanisms of activation and functional regulation of ER Ca²⁺ transporters in the establishment of Ca²⁺ homeostasis. We also contextualize the aberrant alterations of these transporters in carcinogenesis, presenting Ca²⁺-based therapeutic interventions as a means to tackle malignancies.