All of them have been demonstrated to be important in the development of HCC before,9, 10, 19including DEN-induced mouse HCC.27, 28, 29 Accordingly, and in line with our data showing JNK activation and P21 reduction in SMAD7 KO tumors, it was described before that activation of proproliferative JNK signaling is a prerequisite of P21 downregulation and HCC cell proliferation in human tumor cells and in chemically induced mouse liver cancer.19 However, we could not confirm accompanying c-MYC downregulation. Here, MAPK8 is linked to hepatocellular carcinoma.