Overexpressed IGF-2 and IGF-1R are frequently detected in HCC tissues and correlate with advanced stage and prognosis of HCC patients.123–126 Interestingly, although IGF-IR has no nuclear localization sequence and is normally localized to the cytoplasmic membrane, it can undergo nuclear ectoposition by SUMOylation, binding to promoter DNA of its own gene and some oncogene-related genes, such as JUN and FAM21, to promote gene expression.123,127,128 IGF-2R is considered to harbor tumor suppressor gene properties due to inhibition of IGF-1R signaling caused by competitive binding of IGF2. This evidence concerns the gene IGF2R and hepatocellular carcinoma.