Figure 7.

Cartoon depicting relative response of HCC in the Met-β-catenin mice to c-MET or β-catenin suppression. Eleven percent of all human HCCs shows concomitant β-catenin mutations and c-MET overexpression or activation. Coexpression of these two proto-oncogenes in mouse liver leads to HCC, which molecularly resembles the subset of human HCC with simultaneous β-catenin mutations and c-MET activation. When treated with c-MET inhibitors after tumors were established, only a marginal effect on overall HCC burden was observed. However, suppression of β-catenin led to a profound response, and tumors were notably eliminated in a predominant subset of mice. It is anticipated that HCC in this model may respond even more profoundly to combined c-MET and β-catenin suppression, although it has not been directly investigated yet.