SMAD4 and neoplasm: TGF-β regulates tumor initiation, progression, and metastasis via its signaling pathway involving membrane receptors and SMAD transcription factors.68 The dual role of TGF-β in cancer, both as a tumor suppressor and tumor promoter, has been well defined.69 Several lines of evidence demonstrate that pancreatic cancer is clearly linked to TGF-β.70 In particular, SMAD4, a component of the TGF-β pathway, is mutated in approximately 50% of pancreatic cancers.71