Serine-threonine Kinase Receptor-Associated Protein is a Critical Mediator of APC Mutation-Induced Intestinal Tumorigenesis Through a Feed-Forward Mechanism.
Animals
Cell Proliferation
Cell Transformation, Neoplastic
/ genetics
Colorectal Neoplasms
/ genetics
Disease Progression
Extracellular Signal-Regulated MAP Kinases
/ metabolism
Feedback, Physiological
Gene Expression Regulation, Neoplastic
Genes, APC
HT29 Cells
Humans
Mice, Inbred C57BL
Mice, Knockout
Mitogen-Activated Protein Kinase Kinases
/ metabolism
Mutation
RNA-Binding Proteins
/ genetics
Tumor Cells, Cultured
Wnt Signaling Pathway
Intestinal Cancer
Mouse Models
Tumorigenesis
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
29
12
2020
revised:
16
08
2021
accepted:
21
09
2021
pubmed:
15
9
2021
medline:
19
1
2022
entrez:
14
9
2021
Statut:
ppublish
Résumé
Inactivation of the Apc gene is a critical early event in the development of sporadic colorectal cancer (CRC). Expression of serine-threonine kinase receptor-associated protein (STRAP) is elevated in CRCs and is associated with poor outcomes. We investigated the role of STRAP in Apc mutation-induced intestinal tumor initiation and progression. We generated Strap intestinal epithelial knockout mice (Strap Strap deficiency extended the average survival of Apc STRAP is a target of, and is required in, Apc mutation/deletion-induced intestinal tumorigenesis through a novel feed-forward STRAP/MEK-ERK/Wnt-β-catenin/STRAP regulatory axis.
Sections du résumé
BACKGROUND & AIMS
Inactivation of the Apc gene is a critical early event in the development of sporadic colorectal cancer (CRC). Expression of serine-threonine kinase receptor-associated protein (STRAP) is elevated in CRCs and is associated with poor outcomes. We investigated the role of STRAP in Apc mutation-induced intestinal tumor initiation and progression.
METHODS
We generated Strap intestinal epithelial knockout mice (Strap
RESULTS
Strap deficiency extended the average survival of Apc
CONCLUSIONS
STRAP is a target of, and is required in, Apc mutation/deletion-induced intestinal tumorigenesis through a novel feed-forward STRAP/MEK-ERK/Wnt-β-catenin/STRAP regulatory axis.
Identifiants
pubmed: 34520730
pii: S0016-5085(21)03489-2
doi: 10.1053/j.gastro.2021.09.010
pmc: PMC8678216
mid: NIHMS1740081
pii:
doi:
Substances chimiques
RNA-Binding Proteins
0
STRAP protein, human
0
STRAP protein, mouse
0
Extracellular Signal-Regulated MAP Kinases
EC 2.7.11.24
Mitogen-Activated Protein Kinase Kinases
EC 2.7.12.2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
193-208Subventions
Organisme : NCI NIH HHS
ID : U54 CA118638
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA013148
Pays : United States
Organisme : BLRD VA
ID : I01 BX005143
Pays : United States
Organisme : BLRD VA
ID : I01 BX003497
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA095195
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA118623
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA118948
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022. Published by Elsevier Inc.
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