Besides antagonizing IGF-1R, IGF-2R promotes the transport of lysosomal enzymes and the tumor suppressor TGF-β1 into cells to exert inhibitory effects on tumor development.122,129 Thus, in contrast to the overexpression of IGF-1R in patients, the locus where the IGF-2R gene resides has been found to have frequent loss of heterozygosity (LOH) and reduced expression in different cancers, especially HCC.130–132. Here, TGFB1 is linked to hepatocellular carcinoma.