Indeed, while the tumor-suppressive functions of SMAD4 are well established in mediating cell cycle arrest and apoptosis, it is clear that SMAD4 is also required for tumor progression, notably by mediating TGFβ-induced expression of EMT transcription factors, such as SNAIL, SLUG, TWIST and ZEB [33,38,39,40]. This evidence concerns the gene SMAD4 and neoplasm.