ArticleScientific reports2022
Robo4 is constitutively shed by ADAMs from endothelial cells and the shed Robo4 functions to inhibit Slit3-induced angiogenesis.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- In vitro multi-organ invasion model for exploring cardiac resistance to cancer metastasis.Nature communications · 2026Article
- Leveraging in-silico deep learning and computational analyses to predict the pathogenicity of ROBO4 variants of uncertain significance in aortic aneurysm and dissection patients.BMC cardiovascular disorders · 2026Article
- MMP2 sheds Glypican-4 to suppress Slit3-Robo4 signaling and angiogenesis.Proteoglycan research · 2026Article
- A Disintegrin and Metalloproteinase 10 Regulates Ephrin B2-Mediated Endothelial Cell Sprouting and Ischemic Retinopathy.The American journal of pathology · 2025Article
- Article
- Novel Potential Therapeutic Targets in Autosomal Dominant Polycystic Kidney Disease from the Perspective of Cell Polarity and Fibrosis.Biomolecules & therapeutics · 2024Review
- The Role of SLIT3-ROBO4 Signaling in Endoplasmic Reticulum Stress-Induced Delayed Corneal Epithelial and Nerve Regeneration.Investigative ophthalmology & visual science · 2024Article
- P38 MAPK activated ADAM17 mediates ACE2 shedding and promotes cardiac remodeling and heart failure after myocardial infarction.Cell communication and signaling : CCS · 2023Article
- Development of a basement membrane gene signature and identification of the potential candidate therapeutic targets for pancreatic cancer.Gland surgery · 2023Article
- Abnormal expression ofPeerJ · 2023Article
- Immunomodulatory role of metalloproteinase ADAM17 in tumor development.Frontiers in immunology · 2022Review
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Roundabout 4 (Robo4) is a transmembrane receptor that expresses specifically in endothelial cells. Soluble Robo4 was reported in the human plasma and mouse serum and is inhibitory towards FGF- and VEGF-induced angiogenesis. It remains unknown how soluble Robo4 is generated and if soluble Robo4 regulates additional angiogenic signaling. Here, we report soluble Robo4 is the product of constitutive ectodomain shedding of endothelial cell surface Robo4 by disintegrin metalloproteinases ADAM10 and ADAM17 and acts to inhibit angiogenic Slit3 signaling. Meanwhile, the ligand Slit3 induces cell surface receptor Robo4 endocytosis to shield Robo4 from shedding, showing Slit3 inhibits Robo4 shedding to enhance Robo4 signaling. Our study delineated ADAM10 and ADAM17 are Robo4 sheddases, and ectodomain shedding, including negative regulation by its ligand Slit3, represents a novel control mechanism of Robo4 signaling in angiogenesis.
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Registered trials
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