Cross-Talk Between the Adenylyl Cyclase/cAMP Pathway and Ca²⁺ Homeostasis

Cyclic AMP and Ca²⁺ 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, Ca²⁺, as energy, can neither be created nor be destroyed; Ca²⁺ can only be transported, from one compartment to another, or chelated by a variety of Ca²⁺-binding molecules. The fine regulation of cytosolic concentrations of cAMP and free Ca²⁺ 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 Ca²⁺ homeostasis remodeling have been described in cancer cells. In those tumoral cells, cAMP and Ca²⁺ 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 Ca²⁺ intracellular pathways with special attention to the functional and reciprocal regulation between Orai1 and AC8 in normal and cancer cells.