ArticlePloS one2015
TIMP-2 Interaction with MT1-MMP Activates the AKT Pathway and Protects Tumor Cells from Apoptosis.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
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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
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Pooled it
- Targeting matrix metalloproteinase-14 disrupts DNA repair and reduces viability in adrenocortical carcinoma.bioRxiv : the preprint server for biology · 2026Article
- Article
- Mmp14-dependent remodeling of the pericellular-dermal collagen interface governs fibroblast survival.The Journal of cell biology · 2024Article
- MicroRNA 429 regulates MMPs expression by modulating TIMP2 expression in colon cancer cells and inflammatory colitis.Genes & genomics · 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
- MT1-MMP as a Key Regulator of Metastasis.Cells · 2023Review
- The Nonproteolytic Intracellular Domain of Membrane-Type 1 Matrix Metalloproteinase Coordinately Modulates Abdominal Aortic Aneurysm and Atherosclerosis in Mice-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2022Article
- Article
- Human Malignant Rhabdoid Tumor Antigens as Biomarkers and Potential Therapeutic Targets.Cancers · 2022Article
- Unravelling the distinct biological functions and potential therapeutic applications of TIMP2 in cancer.Carcinogenesis · 2022Review
- A Disintegrin and Metalloproteinase (ADAM) Family-Novel Biomarkers of Selected Gastrointestinal (GI) Malignancies?Cancers · 2022Review
- Dynamic transcriptome and chromatin architecture in granulosa cells during chicken folliculogenesis.Nature communications · 2022Article
- The Biology and Function of Tissue Inhibitor of Metalloproteinase 2 in the Lungs.Pulmonary medicine · 2022Review
- Matrix metalloproteinase‑1 expression is regulated by HIF‑1‑dependent and epigenetic mechanisms and serves a tumor‑suppressive role in gastric cancer progression.International journal of oncology · 2021Article
- Membrane-type 1 Matrix Metalloproteinase Modulates Tissue Homeostasis by a Non-proteolytic Mechanism.iScience · 2020Article
- Matrix metalloproteinase-14 (MMP-14) downregulation inhibits esophageal squamous cell carcinoma cell migration, invasion, and proliferation.Thoracic cancer · 2020Article
- Increased matrix metalloproteinases expression in tuberous sclerosis complex: modulation by microRNA 146a and 147b in vitro.Neuropathology and applied neurobiology · 2020Article
- Matrisome-Associated Gene Expression Patterns Correlating with TIMP2 in Cancer.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Membrane-type 1 matrix metalloproteinase (MT1-MMP), a transmembrane proteinase with an extracellular catalytic domain and a short cytoplasmic tail, degrades a variety of extracellular matrix (ECM) components. In addition, MT1-MMP activates intracellular signaling through proteolysis-dependent and independent mechanisms. We have previously shown that binding of tissue inhibitor of metalloproteinases-2 (TIMP-2) to MT1-MMP controls cell proliferation and migration, as well as tumor growth in vivo by activating the Ras-extracellular signal regulated kinase-1 and -2 (ERK1/2) pathway through a mechanism that requires the cytoplasmic but not the proteolytic domain of MT1-MMP. Here we show that in MT1-MMP expressing cells TIMP-2 also induces rapid and sustained activation of AKT in a dose- and time-dependent manner and by a mechanism independent of the proteolytic activity of MT1-MMP. Fibroblast growth factor receptor-1 mediates TIMP-2 induction of ERK1/2 but not of AKT activation; however, Ras activation is necessary to transduce the TIMP-2-activated signal to both the ERK1/2 and AKT pathways. ERK1/2 and AKT activation by TIMP-2 binding to MT1-MMP protects tumor cells from apoptosis induced by serum starvation. Conversely, TIMP-2 upregulates apoptosis induced by three-dimensional type I collagen in epithelial cancer cells. Thus, TIMP-2 interaction with MT1-MMP provides tumor cells with either pro- or anti-apoptotic signaling depending on the extracellular environment and apoptotic stimulus.
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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.