Tumor suppressors govern insulin-like growth factor signaling pathways: implications in metabolism and cancer

Oncogene. 2012 May 31;31(22):2703-14. doi: 10.1038/onc.2011.447. Epub 2011 Oct 3.

Abstract

The insulin-like growth factor (IGF) axis mediates growth, differentiation and developmental processes, and is also involved in control of metabolic activities. Deregulation of IGF axis expression and action is linked to a number of pathologies, ranging from metabolic disorders to growth deficits and cancer development. Activation of the IGF signaling pathway is a crucial prerequisite for malignant transformation. In addition, overexpression of the IGF-1 receptor (IGF-1R) constitutes a typical hallmark of most types of cancer. A series of tumor suppressors have been identified whose mechanisms of action involve transcriptional suppression of the IGF-1R gene. These tumor suppressors include the p53/p63/p73 family, breast cancer gene-1, von-Hippel Lindau protein, Wilms' tumor-1 and others. Comprehensive analyses have identified a complex bidirectional interplay between the IGF and tumor-suppressor signaling pathways. These interactions are of major importance in terms of cancer development and may also predict responsiveness to IGF-1R-targeted therapies. Furthermore, the insulin/IGF system has a pivotal role in the regulation of cancer cell metabolism. Deregulation of IGF axis components by mutated tumor-suppressor proteins may lead to metabolic perturbations, with ensuing pathological consequences.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Humans
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism*
  • Signal Transduction*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Tumor Suppressor Proteins
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1