SMAD3 and Hepatic fibrosis: In the chemoresistant colorectal cancer cell line DLD1-5FU-C10, SMAD3/4 inhibition negatively regulated STAT3 activation, suggesting existence of such reciprocal regulation between TGF-β and STAT3 signaling.37 However, TGF-β-independent tumor-suppressive mechanisms of SMAD7 are also very reasonable and would be in line with findings of Schwabe et al.,38 who recently demonstrated that epithelial TGF-β signaling rather is a protecting factor for mouse cholangiocarcinoma than a contributor to liver fibrosis and thus to subsequent HCC development.