Lef1 restricts ectopic crypt formation and tumor cell growth in intestinal adenomas.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_4CC88CEB1BCE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Lef1 restricts ectopic crypt formation and tumor cell growth in intestinal adenomas.
Périodique
Science advances
Auteur⸱e⸱s
Heino S., Fang S., Lähde M., Högström J., Nassiri S., Campbell A., Flanagan D., Raven A., Hodder M., Nasreddin N., Xue H.H., Delorenzi M., Leedham S., Petrova T.V., Sansom O., Alitalo K.
ISSN
2375-2548 (Electronic)
ISSN-L
2375-2548
Statut éditorial
Publié
Date de publication
19/11/2021
Peer-reviewed
Oui
Volume
7
Numéro
47
Pages
eabj0512
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
[Figure: see text].Somatic mutations in APC or CTNNB1 genes lead to aberrant Wnt signaling and colorectal cancer (CRC) initiation and progression via-catenin-T cell factor/lymphoid enhancer binding factor TCF/LEF transcription factors. We found that Lef1 was expressed exclusively in Apc-mutant, Wnt ligand-independent tumors, but not in ligand-dependent, serrated tumors. To analyze Lef1 function in tumor development, we conditionally deleted Lef1 in intestinal stem cells of Apc(fl/fl) mice or broadly from the entire intestinal epithelium of Apc(fl/fl) or Apc(Min/+) mice. Loss of Lef1 markedly increased tumor initiation and tumor cell proliferation, reduced the expression of several Wnt antagonists, and increased Myc proto-oncogene expression and formation of ectopic crypts in Apc-mutant adenomas. Our results uncover a previously unknown negative feedback mechanism in CRC, in which ectopic Lef1 expression suppresses intestinal tumorigenesis by restricting adenoma cell dedifferentiation to a crypt-progenitor phenotype and by reducing the formation of cancer stem cell niches.
Pubmed
Web of science
Open Access
Oui
Création de la notice
03/12/2021 12:34
Dernière modification de la notice
23/11/2022 7:10
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