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• W2117881676 abstract "Gene-environment interactions are so numerous and biologically complicated that it can be challenging to understand their role in cancer. However, dietary fiber and colorectal cancer prevention may represent a tractable model system. Fiber is fermented by colonic bacteria into short-chain fatty acids such as butyrate. One molecular pathway that has emerged involves butyrate having differential effects depending on its concentration and the metabolic state of the cell. Low-moderate concentrations, which are present near the base of colonic crypts, are readily metabolized in the mitochondria to stimulate cell proliferation via energetics. Higher concentrations, which are present near the lumen, exceed the metabolic capacity of the colonocyte. Unmetabolized butyrate enters the nucleus and functions as a histone deacetylase (HDAC) inhibitor that epigenetically regulates gene expression to inhibit cell proliferation and induce apoptosis as the colonocytes exfoliate into the lumen. Butyrate may therefore play a role in normal homeostasis by promoting turnover of the colonic epithelium. Because cancerous colonocytes undergo the Warburg effect, their preferred energy source is glucose instead of butyrate. Consequently, even moderate concentrations of butyrate accumulate in cancerous colonocytes and function as HDAC inhibitors to inhibit cell proliferation and induce apoptosis. These findings implicate a bacterial metabolite with metaboloepigenetic properties in tumor suppression." @default.
• W2117881676 created "2016-06-24" @default.
• W2117881676 creator A5034062222 @default.
• W2117881676 date "2014-02-15" @default.
• W2117881676 modified "2023-10-02" @default.
• W2117881676 title "Molecular Pathways: Gene–Environment Interactions Regulating Dietary Fiber Induction of Proliferation and Apoptosis via Butyrate for Cancer Prevention" @default.
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• W2117881676 doi "https://doi.org/10.1158/1078-0432.ccr-13-2483" @default.
• W2117881676 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3944646" @default.
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• W2117881676 hasPublicationYear "2014" @default.
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