Molecular mechanisms of tumour invasion: regulation by calcium signals.

Intracellular calcium (Ca2+ ) signals are key regulators of multiple cellular functions, both healthy and physiopathological. It is therefore unsurprising that several cancers present a strong Ca2+ homeostasis deregulation. Among the various hallmarks of cancer disease, a particular role is played by metastasis, which has a critical impact on cancer patients' outcome. Importantly, Ca2+ signalling has been reported to control multiple aspects of the adaptive metastatic cancer cell behaviour, including epithelial-mesenchymal transition, cell migration, local invasion and induction of angiogenesis (see Abstract Figure). In this context Ca2+ signalling is considered to be a substantial intracellular tool that regulates the dynamicity and complexity of the metastatic cascade. In the present study we review the spatial and temporal organization of Ca2+ fluxes, as well as the molecular mechanisms involved in metastasis, analysing the key steps which regulate initial tumour spread.