title: Dietary energy balance modulation of epithelial carcinogenesis: a role for IGF-1 receptor signaling and crosstalk.
abstract: Obesity affects more than one third of the U.S. population and is associated with increased risk and/or disease severity for several chronic diseases, including cancer. In contrast, calorie restriction (CR) consistently inhibits cancer across species and cancer types. Differential effects on globally active circulatory proteins, particularly insulin-like growth factor-1 (IGF-1), provide a plausible mechanistic explanation for the energy balance-cancer link. Diet-induced changes in circulating IGF-1 modulate IGF-1R/EGFR activation and downstream signaling to Akt and mTOR. These dietary energy balance effects on signaling ultimately modulate the levels and/or activity of cell cycle regulatory proteins, regulating proliferation, and modulating susceptibility to tumor development. Selective targeting of mTORC1 potently inhibits tumorigenesis in several model systems producing CR mimetic effects. Targeting this and other pathways modulated by dietary energy balance may lead to the development of strategies for cancer chemoprevention and for reversing the effects of obesity on cancer development and progression.
authors.affiliation: Division of Pharmacology and Toxicology, The University of Texas at Austin, Austin, Texas, USA.
authors.forename: Tricia
authors.initials: T
authors.lastname: Moore
authors.forename: L Allyson
authors.initials: LA
authors.lastname: Checkley
authors.forename: John
authors.initials: J
authors.lastname: DiGiovanni
mesh_terms: D000818:Animals; D031204:Caloric Restriction; D002471:Cell Transformation, Neoplastic; D004734:Energy Metabolism / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D017526:Receptor, IGF Type 1; D058570:TOR Serine-Threonine Kinases