ArticleThe Journal of experimental medicine2022
Inhibition of ADAM17 impairs endothelial cell necroptosis and blocks metastasis.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 66 citations in OpenAlex.
- Endothelial ADAM17 facilitates neutrophil migration and pulmonary microvascular permeability in acute lung inflammation.Journal of biomedical science · 2026Article
- Angiocrine factors in tumor microenvironment: bidirectional crosstalk, mechanistic insights, and therapeutic strategies.Journal of translational medicine · 2026Review
- Extracellular matrix and proteolysis: mechanisms driving irreversible changes and shaping cell behavior.The FEBS journal · 2026Review
- Necroptosis is a key contributor to impaired cardiac repair following myocardial infarction.Cell death & disease · 2026Article
- Endothelial cell-derived IGFBP7 suppresses angiogenesis and tumor progression in colorectal cancer via the VAPA-TGF-β1 pathway.Journal of experimental & clinical cancer research : CR · 2026Article
- Leukocytic ADAM10 and ADAM17 modulate disease severity and systemic outcome in bacterial and viral pneumonia.The European respiratory journal · 2026Article
- Loss of ADAM15 prevents necroptosis induction by partial RIPK1 degradation due to enhanced TNF-R1 surface expression and basal caspase-8 activation.Cell communication and signaling : CCS · 2025Article
- ERβ/circAHNAK Axis Inhibits USP10-FMR1 Deubiquitination to Prevent m⁶A-Mediated ADAM17 Decay and Promote Angiogenesis in Clear Cell Renal Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Integrated single-cell genomics, transcriptomics, and pathomics to identify potential biomarkers in muscle-invasive bladder cancer.Translational andrology and urology · 2025Article
- Article
- Gene expression profile of anoikis reveals new subtypes of liver cancer and discovery of therapeutic targets and biomarkers.Scientific reports · 2025Article
- MLKL-mediated endothelial necroptosis drives vascular damage and mortality in systemic inflammatory response syndrome.Cellular & molecular immunology · 2024Article
- Immunotherapy and pan-apoptotic characterization of the tumor microenvironment in gastric cancer (STAD): a single-cell multidimensional analysis.Discover oncology · 2024Article
- Multi-stage mechanisms of tumor metastasis and therapeutic strategies.Signal transduction and targeted therapy · 2024Review
- Targeting necroptosis: a promising avenue for respiratory disease treatment.Cell communication and signaling : CCS · 2024Review
- Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives.Signal transduction and targeted therapy · 2024Review
- Cryo-EM reveals that iRhom2 restrains ADAM17 protease activity to control the release of growth factor and inflammatory signals.Molecular cell · 2024Article
- Article
- Tumor-derived exosomal ADAM17 promotes pre-metastatic niche formation by enhancing vascular permeability in colorectal cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Oral bacterium Streptococcus mutans promotes tumor metastasis through thrombosis formation.Cancer science · 2024Article
Corrections and comments
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Authors and funding
30 authors at 11 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metastasis is the major cause of death in cancer patients. Circulating tumor cells need to migrate through the endothelial layer of blood vessels to escape the hostile circulation and establish metastases at distant organ sites. Here, we identified the membrane-bound metalloprotease ADAM17 on endothelial cells as a key driver of metastasis. We show that TNFR1-dependent tumor cell-induced endothelial cell death, tumor cell extravasation, and subsequent metastatic seeding is dependent on the activity of endothelial ADAM17. Moreover, we reveal that ADAM17-mediated TNFR1 ectodomain shedding and subsequent processing by the γ-secretase complex is required for the induction of TNF-induced necroptosis. Consequently, genetic ablation of ADAM17 in endothelial cells as well as short-term pharmacological inhibition of ADAM17 prevents long-term metastases formation in the lung. Thus, our data identified ADAM17 as a novel essential regulator of necroptosis and as a new promising target for antimetastatic and advanced-stage cancer therapies.
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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.