Reactivation of the insulin-like growth factor-II signaling pathway in human hepatocellular carcinoma.
Constitutive activation of the insulin-like growth factor (IGF)-signaling axis is frequently observed in human hepatocellular carcinoma (HCC). Especially the overexpression of the fetal growth factor IGF-II, IGF-I receptor (IGF-IR), and cytoplasmic downstream effectors such as insulin-receptor substrates (IRS) contribute to proliferation, anti-apoptosis, and invasive behavior. This review focuses on the relevant alterations in this signaling pathway and independent in vivo models that support the central role IGF-II signaling during HCC development and progression. Since this pathway has become the center of interest as a target for potential anti-cancer therapy in many types of malignancies, various experimental strategies have been developed, including neutralizing antibodies and selective receptor kinase inhibitors, with respect to the specific and efficient reduction of oncogenic IGF-II/IGF-IR-signaling.
Breuhahn
Kai
K
Institute of Pathology, University Hospital of Heidelberg, Heidelberg 69120, Germany. kai.breuhahn@med.uni-heidelberg.de
Schirmacher
Peter
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017451:Receptors, Somatomedin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D017451:Receptors, Somatomedin; D007335:Insulin-Like Growth Factor II