Baek et al. found that altered SMAD3 function occurring in mice heterozygous for the SMAD3 bridging protein SPTBN1 led to fibrosis and spontaneous development of hepatocellular carcinoma (HCC), which was associated with overproliferating endothelial cells, leading to abnormal angiogenesis [60]. This evidence concerns the gene SMAD3 and hepatocellular carcinoma.