MUC13 promotes the development of colitis-associated colorectal tumors via β-catenin activity.
Animals
Antigens, Surface
/ physiology
Apoptosis
Biomarkers, Tumor
/ genetics
Carcinogenesis
Cell Proliferation
Cohort Studies
Colitis
/ chemically induced
Colorectal Neoplasms
/ etiology
Epidermal Growth Factor
/ physiology
Gene Expression Regulation, Neoplastic
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
Mucins
/ genetics
Neoplastic Stem Cells
/ metabolism
Prognosis
Survival Rate
Tumor Cells, Cultured
beta Catenin
/ genetics
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
19
07
2018
accepted:
12
05
2019
revised:
26
02
2019
pubmed:
21
8
2019
medline:
21
3
2020
entrez:
21
8
2019
Statut:
ppublish
Résumé
Many adenocarcinomas, including colorectal cancer (CRC), overexpress the MUC13 cell surface mucin, but the functional significance and mechanisms are unknown. Here, we report the roles of MUC13 in colonic tumorigenesis and tumor progression. High-MUC13 expression is associated with poor survival in two independent patient cohorts. In a comprehensive series of in vivo experiments, we identified a critical role for MUC13 in the development of this malignancy, by promoting survival and proliferation of tumor-initiating cells and driving an immunosuppressive environment that protects tumors from checkpoint inhibitor immunotherapy. In Muc13-deficient mice, fewer tumors are generated after exposure to carcinogens and inflammation, they have markedly reduced β-catenin signaling, have more tumor-infiltrating CD103
Identifiants
pubmed: 31427737
doi: 10.1038/s41388-019-0951-y
pii: 10.1038/s41388-019-0951-y
doi:
Substances chimiques
Antigens, Surface
0
Biomarkers, Tumor
0
Ly64 protein, mouse
0
MUC13 protein, human
0
Mucins
0
beta Catenin
0
Epidermal Growth Factor
62229-50-9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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