Molecular mechanisms of tumour invasion: regulation by calcium signals.

Intracellular calcium (Ca ) signals are key regulators of multiple cellular functions, both healthy and physiopathological. It is therefore unsurprising that several cancers present a strong Ca 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, Ca 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 Ca 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 Ca fluxes, as well as the molecular mechanisms involved in metastasis, analysing the key steps which regulate initial tumour spread.