ArticleOncotarget2016
Interleukin-6 increases matrix metalloproteinase-14 (MMP-14) levels via down-regulation of p53 to drive cancer progression.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Pattern-Based P53 Immunohistochemistry Predicts Recurrence in Colorectal Liver Metastases Without Complete Pathologic Response After Neoadjuvant Chemotherapy.Cancer reports (Hoboken, N.J.) · 2026Article
- Insulin Resistance and Cutaneous Squamous Cell Carcinoma: A Narrative Review of Molecular Mechanisms.Iranian journal of medical sciences · 2026Review
- IL-6 triggers lysosomal degradation of LDL-R and enhances LDL-C uptake in vascular endothelial cells via macropinocytosis.Molecular medicine (Cambridge, Mass.) · 2026Article
- Matrix Metalloproteinase 14 in Corneal Neovascularization.International journal of molecular sciences · 2026Review
- Uncovering the Eyestalk-Androgenic Gland-Testis Regulatory Axis Underlying Male Sexual Development of the Giant Freshwater Prawn Macrobrachium Rosenbergii: Insights from Multi-Tissue Comparative Transcriptomics Analysis.Marine biotechnology (New York, N.Y.) · 2026Article
- Restorative potential of laser-synthesized silver nanoparticles withBeilstein journal of nanotechnology · 2026Article
- Blocking the IL‑6 pathway to treat immune checkpoint inhibitor‑induced inflammatory arthritis (Review).Molecular medicine reports · 2025Review
- The role of MDM2 in angiogenesis: implications for endothelial tip cell formation.In vitro cellular & developmental biology. Animal · 2024Article
- MT1-MMP as a Key Regulator of Metastasis.Cells · 2023Review
- Differential Gene Expression of fresh tissue and patient-derived explants' matricellular proteins augment inflammatory breast cancer metastasis: the possible role of IL-6 and MCP-1.QJM : monthly journal of the Association of Physicians · 2023Article
- Pathophysiology of cellulite: Possible involvement of selective endotoxemia.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2023Review
- A muscle cell-macrophage axis involving matrix metalloproteinase 14 facilitates extracellular matrix remodeling with mechanical loading.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Membrane-type I matrix metalloproteinase (MT1-MMP), lipid metabolism, and therapeutic implications.Journal of molecular cell biology · 2021Review
- p53 Promoted Ferroptosis in Ovarian Cancer Cells Treated with Human Serum Incubated-Superparamagnetic Iron Oxides.International journal of nanomedicine · 2021Article
- The impact of postoperative inflammation on recurrence in patients with colorectal cancer.International journal of clinical oncology · 2020Article
- The Microenvironment of Tongue Cancer.Advances in experimental medicine and biology · 2020Review
- Naringin Protects Against Interleukin 1β (IL-1β)-Induced Human Nucleus Pulposus Cells Degeneration via Downregulation Nuclear Factor kappa B (NF-κB) Pathway and p53 Expression.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- The association of polymorphisms in promoter region of MMP2 and MMP9 with recurrent spontaneous abortion risk in Chinese population.Medicine · 2018Observational
- The Anti-Inflammatory Effects of Vitamin D in Tumorigenesis.International journal of molecular sciences · 2018Review
- Biophysics of Tumor Microenvironment and Cancer Metastasis - A Mini Review.Computational and structural biotechnology journal · 2018Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Matrix metalloproteinases (MMPs) play critical roles in cancer invasion and metastasis by digesting basement membrane and extracellular matrix (ECM). Much attention has focused on the enzymatic activities of MMPs; however, the regulatory mechanism of MMP expression remains elusive. By employing bioinformatics analysis, we identified a potential p53 response element within the MMP-14 promoter. Experimentally, we found that p53 can repress MMP-14 promoter activity, whereas deletion of this p53 response element abrogated this effect. Furthermore, we found that p53 expression decreases MMP-14 mRNA and protein levels and attenuates MMP-14-mediated cellular functions. Additional promoter analysis and chromatin immunoprecipitation studies identified a mechanism of regulation of MMP-14 expression by which p53 and transcription factor Sp1 competitively bind to the promoter. As the correlation between inflammation and cancer aggressiveness is well described, we next sought to evaluate if inflammatory cytokines could differentially affect p53 and MMP-14 levels. We demonstrate that interleukin-6 (IL-6) down-regulates p53 protein levels and thus results in a concomitant increase in MMP-14 expression, leading to enhanced cancer cell invasion and metastasis. Our data collectively indicate a novel mechanism of regulation of MMP-14 by a cascade of IL-6 and p53, demonstrating that the tumor microenvironment directly stimulates molecular changes in cancer cells to drive an invasive phenotype.
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Identifiers
What OpenQuestion holds
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.