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Cited by 15Angiogenesis and VEGF in CancerProtein Structure and DynamicsCell Adhesion Molecules Research

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Structural insight into CD93 recognition by IGFBP7

Open access
Xu, Yueming, Sun, Yi, Zhu, Yuwen, Song, Gaojie·2024·Structure
DOI 10.1016/j.str.2023.12.011PMC PMC12364601

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Abstract

The CD93/IGFBP7 axis proteins are key factors expressed in endothelial cells (EC) that mediate EC angiogenesis and migration. Their upregulation contributes to tumor vascular abnormality and a blockade of this interaction promotes a favorable tumor microenvironment for therapeutic interventions. However, the interactions of these proteins with each other remain unclear. In this study, we determined a partial structure of the human CD93-IGFBP7 complex comprising the EGF 1 domain of CD93 and the IB domain of IGFBP7. Mutagenesis studies confirmed interactions and specificities. Cellular and mouse tumor studies demonstrated the physiological relevance of the CD93-IGFBP7 interaction in EC angiogenesis. Our study provides leads for the development of therapeutic agents to precisely disrupt unwanted CD93-IGFBP7 signaling in the tumor microenvironment. Additionally, analysis of the CD93 full-length architecture provides insights into how CD93 protrudes on the cell surface and forms a flexible platform for binding to IGFBP7 and other ligands.

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Metadata

Authors
Xu, Y., Sun, Y., Zhu, Y., & Song, G.
Affiliations
  • East China Normal University (CN)
  • University of Colorado Anschutz (US)
Corresponding author
  • Zhu, Yuwen
  • Song, Gaojie
ORCID
Venue
Structure
Publisher
Elsevier BV
Published
2024-03
Volume
32
Issue
3
Pages
282-291.e4
ISSN
0969-2126 (ISSN-L)
DOI
10.1016/j.str.2023.12.011
PMC
PMC12364601
OpenAlex
W4390812768
Cited by
15
References
2
Citations by year
2026: 9 · 2025: 4 · 2024: 2
FWCI
2.04
Type
journal article
Language
en
Open access
Licence
Locations
  • Structure (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • SSRN Electronic Journal (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • PubMed Central (submittedVersion)
Funders
  • National Institutes of Health (R01CA258302, R01CA269644, R01CA279398)
  • National Natural Science Foundation of China (32171215)
  • Science and Technology Commission of Shanghai Municipality (21JC1402400)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Keywords
CD93, IGFBP7, ITGAV, protein-protein interaction, tumor microenvironment, ligand specificity, therapeutic targeting

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