This shows that promoter DNA methylation is sufficient to block TGF-β/SMAD3-mediated induction of LBH. Erasure of DNA methylation from VGLL3 failed to restore its TGF-β-dependent induction in HCC-1954, as predicted due to the absence of SMAD3 binding at this locus. This evidence concerns the gene SMAD3 and hepatocellular carcinoma.