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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., Hill, U., Förster, S., Zimmermann, K., Malchin, V., Kühl, A.A., Stein, U., Vieth, M., 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:Adenoma, beta Catenin, CCAAT-Enhancer-Binding Protein-alpha, Caco-2 Cells, Carcinogenesis, Cell Differentiation, Cell Proliferation, Colorectal Neoplasms, Gene Knockout Techniques, HCT116 Cells, Homeostasis, Inbred C57BL Mice, Intestines, Knockout Mice, Neoplastic Gene Expression Regulation, Organoids, Transfection, Tumor Burden, Wnt Signaling Pathway, 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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