Cross-Talk Between the Adenylyl Cyclase/cAMP Pathway and Ca Homeostasis.

Cyclic AMP and Ca are the first second or intracellular messengers identified, unveiling the cellular mechanisms activated by a plethora of extracellular signals, including hormones. Cyclic AMP generation is catalyzed by adenylyl cyclases (ACs), which convert ATP into cAMP and pyrophosphate. By the way, Ca, as energy, can neither be created nor be destroyed; Ca can only be transported, from one compartment to another, or chelated by a variety of Ca-binding molecules. The fine regulation of cytosolic concentrations of cAMP and free Ca is crucial in cell function and there is an intimate cross-talk between both messengers to fine-tune the cellular responses. Cancer is a multifactorial disease resulting from a combination of genetic and environmental factors. Frequent cases of cAMP and/or Ca homeostasis remodeling have been described in cancer cells. In those tumoral cells, cAMP and Ca signaling plays a crucial role in the development of hallmarks of cancer, including enhanced proliferation and migration, invasion, apoptosis resistance, or angiogenesis. This review summarizes the cross-talk between the ACs/cAMP and Ca intracellular pathways with special attention to the functional and reciprocal regulation between Orai1 and AC8 in normal and cancer cells.