The insulin-like growth factor system and cancer.
The insulin-like growth factor (IGF) family of ligands, binding proteins and receptors is an important growth factor system involved in both the development of the organism and the maintenance of normal function of many cells of the body. The system also has powerful anti-apoptotic effects. More recently, evidence has accrued to demonstrate that the IGFs play an important role in cancer. Individuals with serum IGF-II levels in the upper quartile of the normal range (and IGF binding protein-3 levels in the lower quartiles) have a relative risk for developing breast, prostate, colon and lung cancer. IGF-II is commonly expressed by tumor cells and may act as an autocrine growth factor; occasionally even reaching target tissues and causing tumor-induced hypoglycemia. The IGF-I receptor is commonly (though not always) overexpressed in many cancers, and many recent studies have identified new signaling pathways emanating from the IGF-I receptor that affect cancer cell proliferation, adhesion, migration and cell death; functions that are critical for cancer cell survival and metastases. In this review, many aspects of the IGF system and its relationship to cancer will be discussed.
LeRoith
Derek
D
Diabetes Branch, Room 8D12, Building 10, National Institutes of Health MSC 1758, Bethesda, MD 20892-1758, USA. derek@helix.nih.gov
Roberts
Charles T
CT
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D019898:Autocrine Communication; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D019281:Dimerization; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000737:chemistry / Q000502:physiology*; D007335:Insulin-Like Growth Factor II / Q000737:chemistry / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000502:physiology; D009369:Neoplasms / Q000097:blood / Q000209:etiology*; D055503:Protein Multimerization; D017526:Receptor, IGF Type 1 / Q000502:physiology; D017527:Receptor, IGF Type 2 / Q000502:physiology; D011972:Receptor, Insulin / Q000502:physiology; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D018969:Insulin-Like Growth Factor Binding Proteins; D009363:Neoplasm Proteins; D017527:Receptor, IGF Type 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin