Indeed, we show here that EGF-induced Arf6 activation could be suppressed by ectopic expression with GEP100 siRNA as well as GEP100-△PH, so we suggest that the PH domain of GEP100 is involved in EGF signaling to induce Arf6 activation and migration of human hepatoma HepG2 cells. Here, ARF6 is linked to hepatocellular carcinoma.