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

ABSTRACT: We explored the connection between C/EBP? (CCAAT/enhancer-binding protein ?) and Wnt signaling in gut homeostasis and carcinogenesis. C/EBP? 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/EBP? was absent in the nuclear ?-catenin-positive tumor cells. In chemically induced intestinal carcinogenesis, C/EBP? KO in murine gut epithelia increased tumor volume. C/EBP? 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 ?-catenin in organoids attenuated C/EBP? expression, and ectopic C/EBP? expression in HCT116 cells abrogated proliferation. C/EBP? expression accompanied differentiation of the colon cancer cell line Caco-2, whereas ?-catenin stabilization suppressed C/EBP?. These data suggest homeostatic and oncogenic suppressor functions of C/EBP? in the gut by restricting Wnt signaling.

SUBMITTER: Heuberger J 

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

REPOSITORIES: biostudies-literature