The Regulation of Tumor Cell Invasion and Metastasis by Endoplasmic Reticulum-to-Mitochondrial Ca²⁺ Transfer

Cell migration is one of the many processes orchestrated by calcium (Ca²⁺) signaling, and its dysregulation drives the increased invasive and metastatic potential of cancer cells. The ability of Ca²⁺ to function effectively as a regulator of migration requires the generation of temporally complex signals within spatially restricted microdomains. The generation and maintenance of these Ca²⁺ signals require a specific structural architecture and tightly regulated communication between the extracellular space, intracellular organelles, and cytoplasmic compartments. New insights into how Ca²⁺ microdomains are shaped by interorganellar Ca²⁺ communication have shed light on how Ca²⁺ coordinates cell migration by directing cellular polarization and the rearrangement of structural proteins. Importantly, we are beginning to understand how cancer subverts normal migration through the activity of oncogenes and tumor suppressors that impinge directly on the physiological function or expression levels of Ca²⁺ signaling proteins. In this review, we present and discuss research at the forefront of interorganellar Ca²⁺ signaling as it relates to cell migration, metastasis, and cancer progression, with special focus on endoplasmic reticulum-to-mitochondrial Ca²⁺ transfer.