SMAD4 and melanoma: Considering recent findings showing that (a) TGF-β could act of in SMAD2, SMAD3 and SMAD4-independent manner and present pro-oncogenic activity through enhancement of Ras/Raf tumorigenic transformation [49], and (b) majority of examined melanoma cells harbor activating mutation in BRAF and NRAS (BRAF V600E in WM793, 1205Lu, 983B) (NRAS Q61R in WM852), it is likely that TGF-βpromotes tumor progression through the enhancement of SKI-independent pathways, possibly MAP kinases [50].