Molecular Mechanisms of Liver Injury and Hepatocarcinogenesis: Focusing on the Role of Stress-Activated MAPK

Figure 4

Roles of MAP3Ks in controlling the function of stress-activated MAPK and NF-κB in hepatocarcinogenesis. TAK1 can activate NF-κB and JNK, but TAK1 mainly regulates NF-κB activation and acts as a tumor suppressor in hepatocarcinogenesis. ASK1 controls the tumor-suppressing function of JNK and p38 through apoptosis induction and DNA damage response, and thus acts as a tumor suppressor. MEKK1 and MLK3 may be involved in JNK-mediated tumor cell proliferation in hepatocarcinogenesis, but no supporting in vivo evidence exists to support this contention at present. Furthermore, the roles of these molecules may differ according to the disease model and timing.