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A C/EBPα-Wnt connection in gut homeostasis and carcinogenesis

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Item Type:Article
Title:A C/EBPα-Wnt connection in gut homeostasis and carcinogenesis
Creators Name:Heuberger, J. and Hill, U. and Förster, S. and Zimmermann, K. and Malchin, V. and Kühl, A.A. and Stein, U. and Vieth, M. and Birchmeier, W. and Leutz, A.
Abstract:We explored the connection between C/EBPα (CCAAT/enhancer-binding protein α) and Wnt signaling in gut homeostasis and carcinogenesis. C/EBPα was expressed in human and murine intestinal epithelia in the transit-amplifying region of the crypts and was absent in intestinal stem cells and Paneth cells with activated Wnt signaling. In human colorectal cancer and murine APC(Min/+) polyps, C/EBPα was absent in the nuclear β-catenin-positive tumor cells. In chemically induced intestinal carcinogenesis, C/EBPα KO in murine gut epithelia increased tumor volume. C/EBPα deletion extended the S-phase cell zone in intestinal organoids and activated typical proliferation gene expression signatures, including that of Wnt target genes. Genetic activation of β-catenin in organoids attenuated C/EBPα expression, and ectopic C/EBPα expression in HCT116 cells abrogated proliferation. C/EBPα expression accompanied differentiation of the colon cancer cell line Caco-2, whereas β-catenin stabilization suppressed C/EBPα. These data suggest homeostatic and oncogenic suppressor functions of C/EBPα in the gut by restricting Wnt signaling.
Keywords:Animals, Mice
Source:Life Science Alliance
Publisher:Life Science Alliance
Page Range:e201800173
Date:February 2019
Official Publication:https://doi.org/10.26508/lsa.201800173
PubMed:View item in PubMed

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