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

Heuberger J, Hill U, Förster S, Zimmermann K, Malchin V, Kühl AA, Stein U, Vieth M, Birchmeier W, Leutz A (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Life Science Alliance Life Science Alliance

Book Volume: 2

Article Number: e201800173

Journal Issue: 1

DOI: 10.26508/lsa.201800173

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 APCMin/+ 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.

Involved external institutions

Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch DE Germany (DE) Berliner Institut für Gesundheitsforschung (BIH) DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Klinikum Bayreuth DE Germany (DE)

How to cite

APA:

Heuberger, J., Hill, U., Förster, S., Zimmermann, K., Malchin, V., Kühl, A.A.,... Leutz, A. (2019). A C/EBPα–Wnt connection in gut homeostasis and carcinogenesis. Life Science Alliance, 2(1). https://doi.org/10.26508/lsa.201800173

MLA:

Heuberger, Julian, et al. "A C/EBPα–Wnt connection in gut homeostasis and carcinogenesis." Life Science Alliance 2.1 (2019).

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