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Dietary energy balance modulation of epithelial carcinogenesis: a role for IGF‐1 receptor signaling and crosstalk
Author(s) -
Moore Tricia,
Checkley L. Allyson,
DiGiovanni John
Publication year - 2011
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2011.06099.x
Subject(s) - mtorc1 , carcinogenesis , pi3k/akt/mtor pathway , signal transduction , crosstalk , cancer , biology , calorie restriction , cancer research , endocrinology , microbiology and biotechnology , medicine , physics , optics
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.