SMAD4 and neoplasm: Although functional inactivation of Smad4 in colorectal cancer frequently occurs at late stages when tumours acquire invasive and metastatic capabilities, the roles of TGF-β signals in carcinogenesis are complex and also comprise tumour-promoting functions in colorectal carcinogenesis (Muller et al, 2002; Reinacher-Schick et al, 2004).