SMAD4 and neoplasm: Increasing studies have demonstrated that SMAD signaling is essential for TGF-β-induced EMT, and Smad3/Smad4 enhances the induction of EMT by activated TGF-β receptors.45 To conclude, surging lines of evidence indicated SMAD3 played a great role in tumor progression; however, compared to MET, SMAD3-targeted therapy was rarely researched, maybe it needs time to explore the more profound mechanisms in cancers.