The development of a fluorescent Ca2+ biosensor tethered to the N-terminus of the Orai channels allowed the direct detection of the subplasmalemmal Ca2+ increase in a single invadopodium of human melanoma cells due to the activation of SOCE, which resulted in the activation of the Ca2+/CaM-dependent proline-rich tyrosine kinase 2 (Pyk2) [115] plus the c-Src signaling pathway [116], which was essential for starting the invasiveness of these malignant tumors. Here, SRC is linked to cancer.