As an example, CAF derived TGFβ1 activates the smad-2/3 and the beta-catenin signaling pathway within premalignant hepatocytes, which in turn drives multiple cellular processes that are involved in the initiation, growth, survival, migration, differentiation and apoptosis of HCC (Figure 2) [59]. This evidence concerns the gene TGFB1 and hepatocellular carcinoma.