ArticleInternational journal of cancer2010
Timp-2 binding with cellular MT1-MMP stimulates invasion-promoting MEK/ERK signaling in cancer cells.
Article in International journal of cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 39 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- No correlation between TIMP2 -418 G>C polymorphism and increased risk of cancer: evidence from a meta-analysis.PloS one · 2014Pooled it
- Article
- Expression of MMP-2, MMP-9 and TIMP-2 in pituitary tumors and their relationship with cavernous sinus invasion.Endocrine oncology (Bristol, England) · 2025Article
- Nano-Drug Delivery Systems Targeting MMPs: A Promising Treatment for Gliomas.International journal of nanomedicine · 2025Review
- Is Fluoride Blameless?-The Influence of Fluorine Compounds on the Invasiveness of the Human Glioma-like Cell Line U-87.International journal of molecular sciences · 2024Article
- The TIMP protein family: diverse roles in pathophysiology.American journal of physiology. Cell physiology · 2024Review
- Extracellular Proximity Labeling Reveals an Expanded Interactome for the Matrisome Protein TIMP2.Research square · 2024Article
- Cytoplasmic Tail of MT1-MMP: A Hub of MT1-MMP Regulation and Function.International journal of molecular sciences · 2023Review
- Unravelling the distinct biological functions and potential therapeutic applications of TIMP2 in cancer.Carcinogenesis · 2022Review
- Mechanisms underlying melanoma invasion as a consequence of MLK3 loss.Experimental cell research · 2022Article
- The Biology and Function of Tissue Inhibitor of Metalloproteinase 2 in the Lungs.Pulmonary medicine · 2022Review
- Selected Matrix Metalloproteinases (MMP-2, MMP-7) and Their Inhibitor (TIMP-2) in Adult and Pediatric Cancer.Diagnostics (Basel, Switzerland) · 2020Review
- MT4-MMP: The GPI-Anchored Membrane-Type Matrix Metalloprotease with Multiple Functions in Diseases.International journal of molecular sciences · 2019Review
- Harnessing membrane trafficking to promote cancer spreading and invasion: The case of RAB2A.Small GTPases · 2018Review
- Stable expression of α1-antitrypsin Portland in MDA-MB-231 cells increased MT1-MMP and MMP-9 levels, but reduced tumour progression.Journal of cell communication and signaling · 2018Article
- Serum metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in lung carcinoma patients.Journal of thoracic disease · 2017Article
- Article
- Inhibition of MT1-MMP proteolytic function and ERK1/2 signalling influences cell migration and invasion through changes in MMP-2 and MMP-9 levels.Journal of cell communication and signaling · 2017Article
- A pilot study exploring the molecular architecture of the tumor microenvironment in human prostate cancer using laser capture microdissection and reverse phase protein microarray.Molecular oncology · 2016Article
- Less is more: low expression of MT1-MMP is optimal to promote migration and tumourigenesis of breast cancer cells.Molecular cancer · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Both invasion-promoting MT1-MMP and its physiological inhibitor TIMP-2 play a significant role in tumorigenesis and are identified in the most aggressive cancers. Despite its antiproteolytic effects in vitro, clinical data suggest that TIMP-2 expression is positively associated with tumor recurrence, thus emphasizing the wide-ranging role of TIMP-2 in malignancies. To shed light on this role of TIMP-2, we report that low concentrations of TIMP-2, by interacting with MT1-MMP (a specific membrane receptor of TIMP-2), induce the MEK/ERK signaling cascade in fibrosarcoma HT1080 cells which express MT1-MMP naturally. TIMP-2 binding with cell surface-associated MT1-MMP stimulates phosphorylation of MEK1/2, which is upstream of ERK1/2, and the ERK1/2 substrate p90RSK. Consistent with volumes of literature, we confirmed that the activation of ERK stimulated cell migration. Both the transcriptional silencing of MT1-MMP and the inhibition of MEK1/2 reversed the signaling effects of TIMP-2/MT1-MMP while the active site-targeting MMP inhibitor GM6001 did not. Our data suggest that both the interactions of TIMP-2 with MT1-MMP, which activate the pro-migratory ERK signaling cascade,and the conventional inhibition of MT1-MMP's catalytic activity by TIMP-2, play a role in the invasion-promoting function of MT1-MMP. The TIMP-2-induced stimulation of ERK signaling in cancer cells explains the direct, as opposed to the inverse, association of TIMP-2 expression with poor prognosis in cancer.
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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.