Depletion of E-cadherin attenuates the inhibition of Smad3 phosphorylation, resulting in further RBP2 induction and thus constituting the TGF-β1-(p-Smad3)-RBP2-E-cadherin-Smad3 positive feedback regulation circuit that promotes GC malignant progression. The gene discussed is SMAD3; the disease is gastric cancer.