Fig. 8

Working model for HCC migration and invasion controlled by Arf6-driven endocytic recycle of CD147. Arf6 is activated in response to HGF, which is produced in and secreted from liver cancer cells, and promotes CD147 turnover by endocytic recycling. Arf6 activation induces CD147 to highly present at the cell surface and markedly destabilize the junctions at cell-cell contacts, which promote liver cancer cells spreading, migrating, and invading into the ECM. The Arf6 GEF, ARNO, probably activates Arf6 on endosomes, which triggers Rab22 and Rac1 activation (other effectors may also be activated), and subsequently facilitate multiple steps of CD147 trafficking