ArticleOncogene2014
Antibody-directed coupling of endoglin and MMP-14 is a key mechanism for endoglin shedding and deregulation of TGF-β signaling.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 43 citations in OpenAlex.
- Serum Biomarkers in Advanced-Stage AIDS-Associated Kaposi Sarcoma in Resource Limited Settings.Journal of acquired immune deficiency syndromes (1999) · 2026Trial
- A phase I/II study of preoperative letrozole, everolimus, and carotuximab in stage 2 and 3 hormone receptor-positive and Her2-negative breast cancer.Breast cancer research and treatment · 2023Trial
- Anti-endoglin monoclonal antibody TRC105 prevents the increase of liver inflammatory biomarkers in a mouse model of cholestasis.Cellular and molecular life sciences : CMLS · 2026Article
- Assessment of soluble thrombomodulin and soluble endoglin as endothelial dysfunction biomarkers in seriously ill surgical septic patients: correlation with organ dysfunction and disease severity.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2024Article
- Cross-Talk between Mucosal-Associated Invariant T, Natural Killer, and Natural Killer T Cell Populations is Implicated in the Pathogenesis of Placenta Accreta Spectrum.Inflammation · 2023Article
- High concentrations of soluble endoglin can inhibit BMP9 signaling in non-endothelial cells.Scientific reports · 2023Article
- Regulation and Release of Vasoactive Endoglin by Brain Endothelium in Response to Hypoxia/Reoxygenation in Stroke.International journal of molecular sciences · 2022Article
- Kinetics of Biomarkers of Oxidative Stress in Septic Shock: A Pilot Study.Antioxidants (Basel, Switzerland) · 2022Article
- Soluble Endoglin Stimulates Inflammatory and Angiogenic Responses in Microglia That Are Associated with Endothelial Dysfunction.International journal of molecular sciences · 2022Article
- Monoclonal anti-endoglin antibody TRC105 (carotuximab) prevents hypercholesterolemia and hyperglycemia-induced endothelial dysfunction in human aortic endothelial cells.Frontiers in medicine · 2022Article
- Endoglin in the Spotlight to Treat Cancer.International journal of molecular sciences · 2021Review
- Membrane and soluble endoglin role in cardiovascular and metabolic disorders related to metabolic syndrome.Cellular and molecular life sciences : CMLS · 2021Review
- Endoglin Targeting: Lessons Learned and Questions That Remain.International journal of molecular sciences · 2020Review
- Analysis of vascular-associated factors and the prognosis of poorly differentiated hypopharyngeal carcinoma.Oncology letters · 2020Article
- MMP-12, Secreted by Pro-Inflammatory Macrophages, Targets Endoglin in Human Macrophages and Endothelial Cells.International journal of molecular sciences · 2019Article
- Soluble endoglin regulates expression of angiogenesis-related proteins and induction of arteriovenous malformations in a mouse model of hereditary hemorrhagic telangiectasia.Disease models & mechanisms · 2018Article
- Article
- Inhibin Is a Novel Paracrine Factor for Tumor Angiogenesis and Metastasis.Cancer research · 2018Article
- Endoglin in human liver disease and murine models of liver fibrosis-A protective factor against liver fibrosis.Liver international : official journal of the International Association for the Study of the Liver · 2018Article
- Release of endothelial cell associated VEGFR2 during TGF-β modulated angiogenesis in vitro.BMC cell biology · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Endoglin is a transforming growth factor β (TGF-β) coreceptor that serves as a prognostic, diagnostic and therapeutic vascular target in human cancer. A number of endoglin ectodomain-targeting antibodies (Abs) can effectively suppress both normal and tumor-associated angiogenesis, but their molecular actions remain poorly characterized. Here we define a key mechanism for TRACON105 (TRC105), a humanized monoclonal Ab in clinical trials for treatment of advanced or metastatic tumors. TRC105, along with several other endoglin Abs tested, enhance endoglin shedding through direct coupling of endoglin and the membrane-type 1 matrix metalloproteinase (MMP)-14 at the cell surface to release the antiangiogenic factor, soluble endoglin (sEng). In addition to this coupling process, endoglin shedding is further amplified by increased MMP-14 expression that requires TRC105 concentration-dependent c-Jun N-terminal kinase (JNK) activation. There were also notable counterbalancing effects on canonical Smad signaling in which TRC105 abrogated both the steady-state and TGF-β-induced Smad1/5/8 activation while augmenting Smad2/3 activation. Interestingly, TRC105-induced sEng and aberrant Smad signaling resulted in an excessive migratory response through enhanced stress fiber formation and disruption of endothelial cell-cell junctions. Collectively, our study defines endoglin shedding and deregulated TGF-β signaling during migration as major mechanisms by which TRC105 inhibits angiogenesis.
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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.