Taken together, the results presented herein unambiguously demonstrate (a), that SKI levels in melanoma cells are not predictive of their tumorigenic, invasive or metastatic propensity, (b), that TGF-β signals lead to rapid degradation of SKI proteins in a proteasome-dependent manner, and (c), that TGF-β induces a efficient SMAD3/4-dependent transcriptional response in melanoma cells despite high expression of c-SKI and SnoN in these cells. This evidence concerns the gene SMAD3 and melanoma.