Lessons from the Endoplasmic Reticulum Ca(2+) Transporters—A Cancer Connection

Ca(2+) is an integral mediator of intracellular signaling, impacting almost every aspect of cellular life. The Ca(2+)-conducting transporters located on the endoplasmic reticulum (ER) membrane shoulder the responsibility of constructing the global Ca(2+) signaling landscape. These transporters gate the ER Ca(2+) release and uptake, sculpt signaling duration and intensity, and compose the Ca(2+) signaling rhythm to accommodate a plethora of biological activities. In this review, we explore the mechanisms of activation and functional regulation of ER Ca(2+) transporters in the establishment of Ca(2+) homeostasis. We also contextualize the aberrant alterations of these transporters in carcinogenesis, presenting Ca(2+)-based therapeutic interventions as a means to tackle malignancies.