USP7 inactivation suppresses APC-mutant intestinal hyperproliferation and tumor development.
APC
LGR5 stem cell
USP7
Wnt signaling
colorectal cancer
Journal
Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300
Informations de publication
Date de publication:
14 02 2023
14 02 2023
Historique:
received:
29
03
2022
revised:
14
12
2022
accepted:
15
12
2022
pubmed:
21
1
2023
medline:
18
2
2023
entrez:
20
1
2023
Statut:
ppublish
Résumé
Adenomatous polyposis coli (APC) mutation is the hallmark of colorectal cancer (CRC), resulting in constitutive WNT activation. Despite decades of research, targeting WNT signaling in cancer remains challenging due to its on-target toxicity. We have previously shown that the deubiquitinating enzyme USP7 is a tumor-specific WNT activator in APC-truncated cells by deubiquitinating and stabilizing β-catenin, but its role in gut tumorigenesis is unknown. Here, we show in vivo that deletion of Usp7 in Apc-truncated mice inhibits crypt hyperproliferation and intestinal tumor development. Loss of Usp7 prolongs the survival of the sporadic intestinal tumor model. Genetic deletion, but not pharmacological inhibition, of Usp7 in Apc
Identifiants
pubmed: 36669491
pii: S2213-6711(22)00605-1
doi: 10.1016/j.stemcr.2022.12.013
pmc: PMC9968985
pii:
doi:
Substances chimiques
Ubiquitin-Specific Peptidase 7
EC 3.4.19.12
beta Catenin
0
USP7 protein, human
EC 3.4.19.12
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
570-584Subventions
Organisme : Medical Research Council
ID : MC_UP_1202/7
Pays : United Kingdom
Organisme : Cancer Research UK
ID : CC2141
Pays : United Kingdom
Organisme : Medical Research Council
ID : CC2141
Pays : United Kingdom
Organisme : Wellcome Trust
ID : CC2141
Pays : United Kingdom
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interests The authors declare no competing interests.
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