The RAS pathway activation can be amplified by suppression of the negative regulators of RAS/MAPK pathway, including RASAL1, DAB2IP, NORE1A, RKIP, and SPRY213,45,46 or by proteasome-dependent degradations of the negative regulators of RAS/MAPK pathway such as RASSF1A and DUSP147 in human HCC. The gene discussed is RASAL1; the disease is hepatocellular carcinoma.