SMAD4 and neoplasm: TGF-β-mediated tumour suppressive effects can be lost during oncogenic development by alterations in TGF-β receptors (mutations or epigenetic alterations), alterations in co-receptors and ligand traps (both necessary for TGF-β presentation to its receptors), Smad4 mutations or alterations in the function of Smad4 antagonists [179,180,181,182,183].