Furthermore, protein arginine N-methyltransferase 6 has been shown to methylate arginine 100 at CRAF and inhibit the former extracellular matrix complex subunit/RAF binding ability, thereby altering the ERK-mediated nuclear transport of pyruvate kinase M2 isoform (PKM2) and reducing sorafenib resistance in HCC cells [166]. Here, RAF1 is linked to hepatocellular carcinoma.