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Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Mar 21, 2008; 14(11): 1690-1698
Published online Mar 21, 2008. doi: 10.3748/wjg.14.1690
Reactivation of the insulin-like growth factor-II signaling pathway in human hepatocellular carcinoma
Kai Breuhahn, Peter Schirmacher
Kai Breuhahn, Peter Schirmacher, Institute of Pathology, University Hospital of Heidelberg, Heidelberg 69120, Germany
Author contributions: Breuhahn K and Schirmacher P wrote this invited review article.
Correspondence to: Kai Breuhahn, Institute of Pathology, University Hospital of Heidelberg, Heidelberg 69120, Germany. kai.breuhahn@med.uni-heidelberg.de
Telephone: +49-6221-562675
Fax: +49-6221-565251
Received: January 19, 2008
Revised: February 15, 2008
Published online: March 21, 2008
Abstract

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-Ireceptor (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.

Keywords: Hepatocellular carcinoma; Insulin-like growth factor-II; Insulin-like growth factor-I receptor; Insulin receptor substrate; Mouse models; Therapy