Bcl9/Bcl9l are critical for Wnt-mediated regulation of stem cell traits in colon epithelium and adenocarcinomas.

Details

Serval ID
serval:BIB_21C8235600F3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Bcl9/Bcl9l are critical for Wnt-mediated regulation of stem cell traits in colon epithelium and adenocarcinomas.
Journal
Cancer Research
Author(s)
Deka J., Wiedemann N., Anderle P., Murphy-Seiler F., Bultinck J., Eyckerman S., Stehle J.C., André S., Vilain N., Zilian O., Robine S., Delorenzi M., Basler K., Aguet M.
ISSN
1538-7445[electronic], 0008-5472[linking]
Publication state
Published
Issued date
2010
Volume
70
Number
16
Pages
6619-6628
Language
english
Abstract
Canonical Wnt signaling plays a critical role in stem cell maintenance in epithelial homeostasis and carcinogenesis. Here, we show that in the mouse this role is critically mediated by Bcl9/Bcl9l, the mammalian homologues of Legless, which in Drosophila is required for Armadillo/beta-catenin signaling. Conditional ablation of Bcl9/Bcl9l in the intestinal epithelium, where the essential role of Wnt signaling in epithelial homeostasis and stem cell maintenance is well documented, resulted in decreased expression of intestinal stem cell markers and impaired regeneration of ulcerated colon epithelium. Adenocarcinomas with aberrant Wnt signaling arose with similar incidence in wild-type and mutant mice. However, transcriptional profiles were vastly different: Whereas wild-type tumors displayed characteristics of epithelial-mesenchymal transition (EMT) and stem cell-like properties, these properties were largely abrogated in mutant tumors. These findings reveal an essential role for Bcl9/Bcl9l in regulating a subset of Wnt target genes involved in controlling EMT and stem cell-related features and suggest that targeting the Bcl9/Bcl9l arm of Wnt signaling in Wnt-activated cancers might attenuate these traits, which are associated with tumor invasion, metastasis, and resistance to therapy.
Keywords
to-mesenchymal transition, catenin-binding protein, beta-catenin, wnt/beta-catenin, colorectal-cancer, breast cancers, small-intestine, up-regulation, target gene, key role
Pubmed
Web of science
Open Access
Yes
Create date
02/09/2010 12:48
Last modification date
20/08/2019 13:58
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