RT Journal Article SR Electronic T1 A C/EBPα–Wnt connection in gut homeostasis and carcinogenesis JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e201800173 DO 10.26508/lsa.201800173 VO 2 IS 1 A1 Julian Heuberger A1 Undine Hill A1 Susann Förster A1 Karin Zimmermann A1 Victoria Malchin A1 Anja A Kühl A1 Ulrike Stein A1 Michael Vieth A1 Walter Birchmeier A1 Achim Leutz YR 2019 UL https://www.life-science-alliance.org/content/2/1/e201800173.abstract AB 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.