Notably, TGF-β signal mediated through MAPK-dependent Linker phosphorylation of Smad2/3 tend to promote fibrogenesis and oncogenesis, while pSmad3C-mediated TGF-β signaling produce tumor suppressive effects, as a result modulation of phospho-domains of receptor-mediated Smads has become a crucial target for therapeutic exploration. This evidence concerns the gene TGFB1 and neoplasm.