| First Author | Heuberger J | Year | 2019 |
| Journal | Life Sci Alliance | Volume | 2 |
| Issue | 1 | Pages | e201800173 |
| PubMed ID | 30599048 | Mgi Jnum | J:285503 |
| Mgi Id | MGI:6391492 | Doi | 10.26508/lsa.201800173 |
| Citation | Heuberger J, et al. (2019) A C/EBPalpha-Wnt connection in gut homeostasis and carcinogenesis. Life Sci Alliance 2(1):e201800173 |
| abstractText | We explored the connection between C/EBPalpha (CCAAT/enhancer-binding protein alpha) and Wnt signaling in gut homeostasis and carcinogenesis. C/EBPalpha 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/EBPalpha was absent in the nuclear beta-catenin-positive tumor cells. In chemically induced intestinal carcinogenesis, C/EBPalpha KO in murine gut epithelia increased tumor volume. C/EBPalpha 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 beta-catenin in organoids attenuated C/EBPalpha expression, and ectopic C/EBPalpha expression in HCT116 cells abrogated proliferation. C/EBPalpha expression accompanied differentiation of the colon cancer cell line Caco-2, whereas beta-catenin stabilization suppressed C/EBPalpha. These data suggest homeostatic and oncogenic suppressor functions of C/EBPalpha in the gut by restricting Wnt signaling. |
