ArticleGastroenterology2011
Notch1 regulates the effects of matrix metalloproteinase-9 on colitis-associated cancer in mice.
Article in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Prognostic value of matrix metalloproteinase-2 protein and matrix metalloproteinase-9 protein in colorectal cancer: a meta-analysis.BMC cancer · 2024Pooled it
- Comprehensive genomic profiling of triple-negative breast cancer metastases identifies role of PKD1 in immunotherapy resistance.The Journal of clinical investigation · 2026Article
- Dynamic precision therapy in chronic gastrointestinal diseases: A focus on gastroesophageal reflux disease and inflammatory bowel disease-A narrative review and conceptual perspective.Therapeutic advances in gastroenterology · 2026Review
- Biomarker discovery for non-invasive diagnosis of inflammatory bowel disease using blood transcriptomics.Frontiers in immunology · 2025Article
- Identification of diagnostic biomarks and immune cell infiltration in ulcerative colitis.Scientific reports · 2023Article
- Olfactomedin-4 deletion exacerbates DSS-induced colitis through a matrix metalloproteinase-9-dependent mechanism.International journal of biological sciences · 2023Article
- Matrix metalloproteinases as biomarkers and therapeutic targets in colitis-associated cancer.Frontiers in oncology · 2023Review
- The immunomodulatory role of matrix metalloproteinases in colitis-associated cancer.Frontiers in immunology · 2022Review
- Insights into the Role of Matrix Metalloproteinases in Precancerous Conditions and in Colorectal Cancer.Cancers · 2021Review
- Excess Provisional Extracellular Matrix: A Common Factor in Bicuspid Aortic Valve Formation.Journal of cardiovascular development and disease · 2021Review
- A Novel PAK1-Notch1 Axis Regulates Crypt Homeostasis in Intestinal Inflammation.Cellular and molecular gastroenterology and hepatology · 2021Article
- Matrix Metalloproteinase-9 (MMP-9) induced disruption of intestinal epithelial tight junction barrier is mediated by NF-κB activation.PloS one · 2021Article
- CircUBAP2 Promotes MMP9-Mediated Oncogenic Effect via Sponging miR-194-3p in Hepatocellular Carcinoma.Frontiers in cell and developmental biology · 2021Article
- Matrix metalloproteinase 9 (MMP9) limits reactive oxygen species (ROS) accumulation and DNA damage in colitis-associated cancer.Cell death & disease · 2020Article
- Role of mTORC1 in intestinal epithelial repair and tumorigenesis.Cellular and molecular life sciences : CMLS · 2019Review
- Matrix metalloproteinase MMP9 maintains epithelial barrier function and preserves mucosal lining in colitis associated cancer.Oncotarget · 2017Article
- Short-term treatment with eicosapentaenoic acid improves inflammation and affects colonic differentiation markers and microbiota in patients with ulcerative colitis.Scientific reports · 2017Article
- Dynamical states, possibilities and propagation of stress signal.Scientific reports · 2017Article
- Article
- Flavonoids Extracted from Licorice Prevents Colitis-Associated Carcinogenesis in AOM/DSS Mouse Model.International journal of molecular sciences · 2016Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsInflammatory bowel disease increases the risks of colon cancer and colitis-associated cancer (CAC). Epithelial cell-derived matrix metalloproteinase (MMP)-9 mediates inflammation during acute colitis and the cleavage and activation of the transcription factor Notch1, which prevents differentiation of progenitor cells into goblet cells. However, MMP-9 also protects against the development of CAC and acts as a tumor suppressor. We investigated the mechanisms by which MMP-9 protects against CAC in mice.
methodsC57/B6 wild-type mice were given a single dose of azoxymethane and 2 cycles of dextran sulfate sodium (DSS). Mice were also given the γ-secretase inhibitor difluorophenacetyl-l-alanyl-S-phenylglycine t-butyl ester (DAPT) or dimethyl sulfoxide (control) during each DSS cycle; they were killed on day 56. We analyzed embryonic fibroblasts isolated from wild-type and MMP-9-/- mice and HCT116 cells that were stably transfected with MMP-9.
resultsWild-type mice were more susceptible to CAC following inhibition of Notch1 by DAPT, shown by increased numbers of tumors and level of dysplasia compared with controls. Inhibition of Notch1 signaling significantly reduced protein levels of active Notch1, p53, p21WAF1/Cip1, Bax-1, active caspase-3, as well as apoptosis, compared with controls. Similar results were observed in transgenic HCT116 cells and embryonic fibroblasts from MMP-9-/- mice on γ-radiation-induced damage of DNA.
conclusionsMMP-9 mediates Notch1 signaling via p53 to regulate apoptosis, cell cycle arrest, and inflammation. By these mechanisms, it might prevent CAC.
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Registered trials
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