title: Tumor suppressors govern insulin-like growth factor signaling pathways: implications in metabolism and cancer.
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.
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. hwerner@post.tau.ac.il
authors.forename: H
authors.initials: H
authors.lastname: Werner
mesh_terms: D000818:Animals; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D025521:Tumor Suppressor Proteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1