In favor of loss of agonist induced MC1R signaling being involved in both pigment-dependent and independent mechanisms, it is known that α-MSH stimulates melanocyte precursor differentiation and inhibits melanocyte and melanoma cell migration in cell culture [22-24], and siRNA depletion of the downstream α-MSH effector, Mitf, increased B16 melanoma cell colonization in lungs [25], although coinjection of α-MSH and murine B16-F1 melanoma cells into mice did not reduce lung tumors [26]. This evidence concerns the gene MITF and melanoma.