TGFB1 and neoplasm: Indeed, while mutations in TGF-β signaling machinery are rare in most cancers, frequent genetic alterations in Smad components characterize gastrointestinal carcinomas (e.g., pancreatic, colorectal) [76–78] and suggest a tumor suppressive and anti-metastatic role of TGF-β pathway in a context dependent manner [79–82].