The mechanosensitive TRPV2 calcium channel controls human melanoma invasiveness and metastatic potential

Discovery of therapeutic targets against metastasis is of primary importance since being the main cause of cancer-related death. Deregulation of calcium homeostasis has been involved in numerous cellular metastatic behaviors, although the molecular determinants supporting these processes remain often unclear. Here, we showed that the expression of the plasma membrane TRPV2 calcium channel is a prominent feature in melanoma progression and dissemination. In fact, TRPV2 activity was sufficient to confer an invasive phenotype to non-invasive melanoma cells. Conversely, the invasive and migratory potential of highly metastatic melanoma cells was abolished upon TRPV2 silencing. Mechanistically, TRPV2 supports melanoma cells aggressiveness by being a new regulator of the calpain-dependent maturation of focal adhesion, and actin cytoskeleton remodeling. Finally, TRPV2 overexpression is a marker of advanced malignancy and bad prognosis in human melanoma tumor samples. Altogether, TRPV2-induced Ca2+ signaling orchestrates in vitro motility and invasiveness of melanoma cells, as well as in vivo metastatic melanoma tumors dissemination.