TY - JOUR T1 - A C/EBPα–Wnt connection in gut homeostasis and carcinogenesis JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201800173 VL - 2 IS - 1 SP - e201800173 AU - Julian Heuberger AU - Undine Hill AU - Susann Förster AU - Karin Zimmermann AU - Victoria Malchin AU - Anja A Kühl AU - Ulrike Stein AU - Michael Vieth AU - Walter Birchmeier AU - Achim Leutz Y1 - 2019/02/01 UR - https://www.life-science-alliance.org/content/2/1/e201800173.abstract N2 - 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. ER -