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

H. Werner*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

108 Scopus citations

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.

Original languageEnglish
Pages (from-to)2703-2714
Number of pages12
JournalOncogene
Volume31
Issue number22
DOIs
StatePublished - 31 May 2012

Funding

FundersFunder number
Insulin-Dependent Diabetes Trust
Israel Cancer Research Fund
United States-Israel Binational Science Foundation
Israel Cancer Association
Israel Science Foundation

    Keywords

    • BRCA1
    • IGF
    • IGF-1 receptor
    • Insulin-like growth factors
    • P53
    • Tumor suppressors

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