In:
Life Science Alliance, Life Science Alliance, LLC, Vol. 2, No. 1 ( 2019-02), p. e201800173-
Abstract:
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 APC Min/+ 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.
Type of Medium:
Online Resource
ISSN:
2575-1077
DOI:
10.26508/lsa.201800173
Language:
English
Publisher:
Life Science Alliance, LLC
Publication Date:
2019
detail.hit.zdb_id:
2948687-7
