SMAD7 and hepatocellular carcinoma: On the other hand, SMAD7 can have TGF-β-independent functions, for example, can interact with several proteins that are not related to TGF-β signaling, thus affecting tumor progression non-canonically.4 In human HCC, Wang et al.5 and Xia et al.6 showed reduced SMAD7 levels in tumor tissue.