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Suppression of Tumorigenicity-14, encoding matriptase, is a critical suppressor of colitis and colitis-associated colon carcinogenesis
- Source :
- Oncogene
- Publication Year :
- 2011
- Publisher :
- Springer Science and Business Media LLC, 2011.
-
Abstract
- Colitis-associated colorectal cancers are an etiologically distinct subgroup of colon cancers that occur in individuals suffering from inflammatory bowel disease and arise as a consequence of persistent exposure of hyperproliferative epithelial stem cells to an inflammatory microenvironment. An intrinsic defect in the intestinal epithelial barrier has been proposed to be one of several factors that contribute to the inappropriate immune response to the commensal microbiota that underlies inflammatory bowel disease. Matriptase is a membrane-anchored serine protease encoded by Suppression of Tumorigenicity-14 (ST14) that strengthens the intestinal epithelial barrier by promoting tight junction formation. Here we show that intestinal epithelial-specific ablation of St14 in mice causes formation of colon adenocarcinoma with very early onset and high penetrance. Neoplastic progression is preceded by a chronic inflammation of the colon that resembles human inflammatory bowel disease and is promoted by the commensal microbiota. This study demonstrates that inflammation-associated colon carcinogenesis can be initiated and promoted solely by an intrinsic intestinal permeability barrier perturbation, establishes St14 as a critical tumor suppressor gene in the mouse gastrointestinal tract, and adds matriptase to the expanding list of pericellular proteases with tumor suppressive functions.
- Subjects :
- Adenoma
Cancer Research
Mice, 129 Strain
Colon
Inflammation
Adenocarcinoma
Inflammatory bowel disease
ST14
Basement Membrane
Epithelium
Gene Expression Regulation, Enzymologic
Article
Intestinal absorption
Mice
Genetics
medicine
Animals
Humans
Genes, Tumor Suppressor
Neoplasm Invasiveness
Matriptase
Colitis
Molecular Biology
beta Catenin
Cell Proliferation
Mice, Knockout
Intestinal permeability
biology
Serine Endopeptidases
Membrane Proteins
Inflammatory Bowel Diseases
medicine.disease
Anti-Bacterial Agents
Gene Expression Regulation, Neoplastic
Mice, Inbred C57BL
Cell Transformation, Neoplastic
Intestinal Absorption
Colonic Neoplasms
Immunology
biology.protein
Metagenome
medicine.symptom
Precancerous Conditions
Signal Transduction
Subjects
Details
- ISSN :
- 14765594 and 09509232
- Volume :
- 31
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....9e7b28a30f5da8087f7c7eb1afc7815e