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 from nuclear -cateninpositive 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. Comparing gene expression of wild type and C/EBP KO organoids by RNA sequencing aimed to identify C/EBP dependent alterations in gene expression. SOURCE: Achim Leutz (aleutz@mdc-berlin.de) - Cell Differentiation and Tumorigenesis MDC Berlin

Pluto Bioinformatics

GSE123925: A C/EBPWnt connection in gut homeostasis and carcinogenesis