Cited by 179Cell Adhesion Molecules ResearchAngiogenesis and VEGF in CancerCellular Mechanics and Interactions

Stable interaction between α5β1 integrin and Tie2 tyrosine kinase receptor regulates endothelial cell response to Ang-1

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Cascone, Ilaria, Napione, Lucia, Maniero, Fabrizio, Serini, Guido, Bussolino, Federico·2005·The Journal of Cell Biology

Abstract

During angiogenic remodeling, Ang-1, the ligand of Tie2 tyrosine kinase, is involved in vessel sprouting and stabilization through unclear effects on nascent capillaries and mural cells. In our study, we hypothesized that the Ang-1/Tie2 system could cross-talk with integrins, and be influenced by the dynamic interactions between extracellular matrix and endothelial cells (ECs). Here, we show that α5β1 specifically sensitizes and modulates Tie2 receptor activation and signaling, allowing EC survival at low concentrations of Ang-1 and inducing persistent EC motility. Tie2 and α5β1 interact constitutively; α5β1 binding to fibronectin increases this association, whereas Ang-1 stimulation recruits p85 and FAK to this complex. Furthermore, we demonstrate that Ang-1 is able to mediate selectively α5β1 outside-in FAK phosphorylation. Thus, Ang-1 triggers signaling pathways through Tie2 and α5β1 receptors that could cross-talk when Tie2/α5β1 interaction occurs in ECs plated on fibronectin. By using blocking antibodies, we consistently found that α5β1, but not αvβ3 activation, is essential to Ang-1–dependent angiogenesis in vivo.

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  1. Max, R., R.R. Gerritsen, P.T. Nooijen, S.L. Goodman, A. Sutter, U. Keilholz, D.J. Ruiter, and R.M. De Waal. 1997. Immunohistochemical analysis of integrin alpha vbeta3 expression on tumor-associated vessels of human carcinomas. Int. J. Cancer. 71: 320–324. 9139861

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Authors
Cascone, I., Napione, L., Maniero, F., Serini, G., & Bussolino, F.
Affiliations
University of Turin (IT)
Corresponding author
Cascone, Ilaria
Venue
The Journal of Cell Biology
Published
2005-09-12
Volume
170
Issue
6
Pages
993-1004
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
OpenAlex
W2115566079
Cited by
179
References
79
Citations by year
2026: 4 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 7 · 2021: 4 · 2020: 6 · 2019: 12 · 2018: 10 · 2017: 10 · 2016: 11 · 2015: 7 · 2014: 6 · 2013: 9 · 2012: 3
FWCI
6.38
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Cell Biology (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • PORTO@Iris (submittedVersion, cc-by-nc-sa)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
Funders
  • Compagnia di San Paolo
  • Ministero della Salute
  • Istituto Superiore di Sanità
  • Associazione Italiana per la Ricerca sul Cancro
  • Regione Piemonte
Topics
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
alpha5beta1 integrin, Tie2 receptor, angiopoietin-1, angiogenesis, endothelial cells, fibronectin, focal adhesion kinase, p85, endothelial cell motility, endothelial cell survival, vessel stabilization
MeSH terms
Animals, Cell Adhesion, Cell Line, Cell Movement, Cell Survival, Chick Embryo, Chromones, Cricetulus, Dose-Response Relationship, Drug, Endothelium, Vascular, Fibrinogen, Fibronectins, Cricetinae, Humans, Kinetics, Morpholines, Precipitin Tests, Umbilical Veins, CHO Cells, Neovascularization, Physiologic, Cell Culture Techniques, Collagen Type I, Integrin alpha5beta1, Angiopoietin-1, Receptor, TIE-2, Chorioallantoic Membrane

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