ArticleOncotarget2017
Epithelial derived-matrix metalloproteinase (MMP9) exhibits a novel defensive role of tumor suppressor in colitis associated cancer by activating MMP9-Notch1-ARF-p53 axis.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 31 citations in OpenAlex.
- Inhibition of matrix metalloproteinase-9 attenuates kidney fibrosis and cellular senescence in the transition from acute kidney injury to chronic kidney disease.Renal failure · 2025Article
- Antioxidant and Anticancer Mechanisms of Unique Polyphenols inMolecules (Basel, Switzerland) · 2025Article
- Computer-Aided Screening and Revealing Action Mechanism of Food-Derived Tripeptides Intervention in Acute Colitis.International journal of molecular sciences · 2022Article
- Chemically Induced Colitis-Associated Cancer Models in Rodents for Pharmacological Modulation: A Systematic Review.Journal of clinical medicine · 2022Review
- MMP9: A Tough Target for Targeted Therapy for Cancer.Cancers · 2022Review
- PRL-3 and MMP9 Expression and Epithelial-Mesenchymal Transition Markers in Circulating Tumor Cells From Patients With Colorectal Cancer: Potential Value in Clinical Practice.Frontiers in oncology · 2022Article
- The research progress in the interaction betweenFrontiers in microbiology · 2022Review
- The immunomodulatory role of matrix metalloproteinases in colitis-associated cancer.Frontiers in immunology · 2022Review
- The correlation of the miR-29a/MMP9 axis withAmerican journal of translational research · 2021Article
- Matrix Metalloproteinase-9 (MMP-9) induced disruption of intestinal epithelial tight junction barrier is mediated by NF-κB activation.PloS one · 2021Article
- Matrix metalloproteinase 9 (MMP9) limits reactive oxygen species (ROS) accumulation and DNA damage in colitis-associated cancer.Cell death & disease · 2020Article
- Role of MMP-9 in epithelial-mesenchymal transition of thyroid cancer.World journal of surgical oncology · 2020Article
- Matrix Metalloproteinase-9 (MMP-9) as a Cancer Biomarker and MMP-9 Biosensors: Recent Advances.Sensors (Basel, Switzerland) · 2018Review
- Matrix metalloproteinase MMP9 maintains epithelial barrier function and preserves mucosal lining in colitis associated cancer.Oncotarget · 2017Article
- Evaluation of salivary MMP-9 in oral squamous cell carcinoma and oral leukoplakia using ELISA.Journal of oral and maxillofacial pathology : JOMFPArticle
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Colitis associated cancer (CAC) is chronic inflammation driven colon cancer, prevalent among individuals with Inflammatory Bowel Disease. Matrix-metalloproteinase (MMP9) is one of the essential regulators of extra cellular matrix components. We have shown that MMP9 is protective in CAC contrary to its inflammatory role in acute-colitis. Aim of our study is to identify the mechanism of the protective role of epithelial derived-MMP9 in CAC. We used homozygous transgenic mice constitutively-expressing MMP9 in colonic-epithelium (TgM9) and wild-type (WT) littermates for in vivo experiments. Stably-transfected HCT116 with/without MMP9, and mouse embryonic-fibroblasts (WT and MMP9-/-, MEFs) were used for in vitro experiments. TgM9 mice exhibited less tumor burden, increased apoptosis, and increased expressions of active-Notch1, p53, p21WAF1/Cip1, caspase-3 and cyclin E in CAC compared to WTs. These results were supported by MEFs data. HCT116-cells overexpressing MMP9 indicated decreased cell proliferation, S-phase cell-cycle arrest and less DNA damage compared to vector. MMP9-/- mice showed attenuation of MMP9 was directly associated with p19ARF. Our study identifies the tumor suppressor role of epithelial derived-MMP9 in CAC via novel mechanistic pathway "MMP9-Notch1-ARF-p53 axis" regulating apoptosis, cell-cycle arrest and DNA damage implying, that MMP9 expression might be a natural/biological way to suppress colonic ulceration due to chronic inflammation.
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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.