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

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/EBP

SUBMITTER: Heuberger J 

PROVIDER: S-EPMC6306571 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature