Remodelling of Ca2+ transport in cancer: how it contributes to cancer hallmarks?

Cancer involves defects in the mechanisms underlying cell proliferation, death and migration. Calcium ions are central to these phenomena, serving as major signalling agents with spatial localization, magnitude and temporal characteristics of calcium signals ultimately determining cell''s fate. Cellular Ca²⁺ signalling is determined by the concerted action of a molecular Ca²⁺-handling toolkit which includes: active energy-dependent Ca²⁺ transporters, Ca²⁺-permeable ion channels, Ca²⁺-binding and storage proteins, Ca²⁺-dependent effectors. In cancer, because of mutations, aberrant expression, regulation and/or subcellular targeting of Ca²⁺-handling/transport protein(s) normal relationships among extracellular, cytosolic, endoplasmic reticulum and mitochondrial Ca²⁺ concentrations or spatio-temporal patterns of Ca²⁺ signalling become distorted. This causes deregulation of Ca²⁺-dependent effectors that control signalling pathways determining cell''s behaviour in a way to promote pathophysiological cancer hallmarks such as enhanced proliferation, survival and invasion. Despite the progress in our understanding of Ca²⁺ homeostasis remodelling in cancer cells as well as in identification of the key Ca²⁺-transport molecules promoting certain malignant phenotypes, there is still a lot of work to be done to transform fundamental findings and concepts into new Ca²⁺ transport-targeting tools for cancer diagnosis and treatment.