ArticleCancer research2010
Matrix metalloproteinase-9 functions as a tumor suppressor in colitis-associated cancer.
Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 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
- Impairment of Hyaluronan-Related Glycocalyx Inhibits Macropinocytosis in Cancer Cells via p21 Upregulation.Biomacromolecules · 2025Article
- Review
- Enhancing Anti-Tumorigenic Efficacy of Eugenol in Human Colon Cancer Cells Using Enzyme-Responsive Nanoparticles.Cancers · 2023Article
- Matrix metalloproteinases as biomarkers and therapeutic targets in colitis-associated cancer.Frontiers in oncology · 2023Review
- An innate IL-25-ILC2-MDSC axis creates a cancer-permissive microenvironment forScience immunology · 2022Article
- MMP9: A Tough Target for Targeted Therapy for Cancer.Cancers · 2022Review
- Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation.Frontiers in cellular neuroscience · 2022Article
- The immunomodulatory role of matrix metalloproteinases in colitis-associated cancer.Frontiers in immunology · 2022Review
- Emerging roles for IL-25 and IL-33 in colorectal cancer tumorigenesis.Frontiers in immunology · 2022Review
- Insights into the Role of Matrix Metalloproteinases in Precancerous Conditions and in Colorectal Cancer.Cancers · 2021Review
- An Up-Scalable and Cost-Effective Methodology for Isolating a Polypeptide Matrix Metalloproteinase-9 Inhibitor fromFoods (Basel, Switzerland) · 2021Article
- Comprehensive Analysis of the Expression and Prognosis for MMPs in Human Colorectal Cancer.Frontiers in oncology · 2021Article
- Matrix metalloproteinase 9 (MMP9) limits reactive oxygen species (ROS) accumulation and DNA damage in colitis-associated cancer.Cell death & disease · 2020Article
- Relationship between serum MMP-9 level and prognosis after radical resection for Hilar cholangiocarcinoma patients.Acta cirurgica brasileira · 2019Article
- Matrix Metalloproteinase-9 (MMP-9) as a Cancer Biomarker and MMP-9 Biosensors: Recent Advances.Sensors (Basel, Switzerland) · 2018Review
- A Potential Role for MMPs during the Formation of Non-Neurogenic Placodes.Journal of developmental biology · 2018Review
- Article
- Matrix metalloproteinase MMP9 maintains epithelial barrier function and preserves mucosal lining in colitis associated cancer.Oncotarget · 2017Article
- Mechanisms of colitis-accelerated colon carcinogenesis and its prevention with the combination of aspirin and curcumin: Transcriptomic analysis using RNA-seq.Biochemical pharmacology · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
There is a well-documented association of matrix metalloproteinase-9 (MMP-9) and receptor Notch-1 overexpression in colon cancer. We recently showed that MMP-9 is also upregulated in colitis, where it modulates tissue damage and goblet cell differentiation via proteolytic cleavage of Notch-1. In this study, we investigated whether MMP-9 is critical for colitis-associated colon cancer (CAC). Mice that are wild type (WT) or MMP-9 nullizygous (MMP-9(-/-)) were used for in vivo studies and the human enterocyte cell line Caco2-BBE was used for in vitro studies. CAC was induced in mice using an established carcinogenesis protocol that involves exposure to azoxymethane followed by treatment with dextran sodium sulfate. MMP-9(-/-) mice exhibited increased susceptibility to CAC relative to WT mice. Elevations in tumor multiplicity, size, and mortality were associated with increased proliferation and decreased apoptosis. Tumors formed in MMP-9(-/-) mice exhibited expression of p21(WAF1/Cip1) and increased expression of beta-catenin relative to WT mice. In vitro studies of MMP-9 overexpression showed increased Notch-1 activation with a reciprocal decrease in beta-catenin. Notch and beta-catenin/Wnt signaling have crucial roles in determining differentiation and carcinogenesis in gut epithelia. Despite being a mediator of proinflammatory responses in colitis, MMP-9 plays a protective role and acts as a tumor suppressor in CAC by modulating Notch-1 activation, thereby resulting in activation of p21(WAF1/Cip1) and suppression of beta-catenin.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.