Fig. 6

Schematic representation of YAP-mediated modulation of liver carcinogenesis. A Activation of YAP in damaged hepatocytes protects against liver carcinogenesis by activating the GTPases RAC and CDC42, which regulate cytoskeletal organization. Activation of CDC42 and Rac drives migration of damaged hepatocytes to sinusoids, where they are eliminated by KCs. B YAP acts as a trigger of liver carcinogenesis under the condition of impaired autophagy, which affects cell clearance leading to accumulation of YAP due to decreased lysosomal-mediated degradation of YAP. C A mechanism of tumor suppression by YAP and TAZ based on a competitive interaction between tumor cells (TCs) and their environment has been described. Deletion of Yap/Taz in peritumoral cells (PTCs) accelerates tumor growth, whereas its overexpression suppresses tumor growth and can cause tumor regression. When competition is neutralized, e.g., when PTCs and TCs simultaneously overexpress or delete Yap/Taz, the tumor burden is similar to that in WT liver. Thus, tumor cells require YAP/TAZ for survival, but only when surrounded by WT hepatocytes