ArticleThe Journal of clinical investigation2012
Endothelial epsin deficiency decreases tumor growth by enhancing VEGF signaling.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 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.
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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
83 citing papers in PubMed, 113 citations in OpenAlex.
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- Endocytic Adaptor Proteins in Vascular Diseases: Critical Role of Intracellular Trafficking in Regulating Pathobiology of Vascular Disorders.Cardiology discovery · 2026Review
- D-mannose suppresses the angiogenesis and progression of colorectal cancer.Acta biochimica et biophysica Sinica · 2025Article
- Epsin3 promotes non-small cell lung cancer progression via modulating EGFR stability.Cell & bioscience · 2025Article
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- Elucidating the crosstalk between endothelial-to-mesenchymal transition (EndoMT) and endothelial autophagy in the pathogenesis of atherosclerosis.Vascular pharmacology · 2024Review
- Eph-ephrin signaling couples endothelial cell sorting and arterial specification.Nature communications · 2024Article
- Epsin Endocytic Adaptor Proteins in Angiogenic and Lymphangiogenic Signaling.Cold Spring Harbor perspectives in medicine · 2024Review
- Metamorphic Effect of Angiogenic Switch in Tumor Development: Conundrum of Tumor Angiogenesis Toward Progression and Metastatic Potential.Biomedicines · 2023Review
- Protein post-translational modifications in the regulation of cancer hallmarks.Cancer gene therapy · 2023Review
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- Epsin Nanotherapy Regulates Cholesterol Transport to Fortify Atheroma Regression.Circulation research · 2023Article
- Differentially hypomethylated cell-free DNA and coronary collateral circulation.Clinical epigenetics · 2022Article
- Cysteine oxidation of copper transporter CTR1 drives VEGFR2 signalling and angiogenesis.Nature cell biology · 2022Article
- Examining SNP-SNP interactions and risk of clinical outcomes in colorectal cancer using multifactor dimensionality reduction based methods.Frontiers in genetics · 2022Article
- Trelagliptin ameliorates oxygen-glucose deprivation/reperfusion (OGD/R)-induced mitochondrial dysfunction and metabolic disturbance of endothelial cells.Human cell · 2021Article
- Endocytosis in the context-dependent regulation of individual and collective cell properties.Nature reviews. Molecular cell biology · 2021Review
23 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 4 institutions in 2 countries.
Funding
Abstract
Epsins are a family of ubiquitin-binding, endocytic clathrin adaptors. Mice lacking both epsins 1 and 2 (Epn1/2) die at embryonic day 10 and exhibit an abnormal vascular phenotype. To examine the angiogenic role of endothelial epsins, we generated mice with constitutive or inducible deletion of Epn1/2 in vascular endothelium. These mice exhibited no abnormal phenotypes under normal conditions, suggesting that lack of endothelial epsins 1 and 2 did not affect normal blood vessels. In tumors, however, loss of epsins 1 and 2 resulted in disorganized vasculature, significantly increased vascular permeability, and markedly retarded tumor growth. Mechanistically, we show that VEGF promoted binding of epsin to ubiquitinated VEGFR2. Loss of epsins 1 and 2 specifically impaired endocytosis and degradation of VEGFR2, which resulted in excessive VEGF signaling that compromised tumor vascular function by exacerbating nonproductive leaky angiogenesis. This suggests that tumor vasculature requires a balance in VEGF signaling to provide sufficient productive angiogenesis for tumor development and that endothelial epsins 1 and 2 negatively regulate the output of VEGF signaling. Promotion of excessive VEGF signaling within tumors via a block of epsin 1 and 2 function may represent a strategy to prevent normal angiogenesis in cancer patients who are resistant to anti-VEGF 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.