Article (Scientific journals)
Suppression of beta3-integrin in mice triggers a neuropilin-1-dependent change in focal adhesion remodelling that can be targeted to block pathological angiogenesis.
Ellison, Tim S.; Atkinson, Samuel J.; Steri, Veronica et al.
2015In Disease Models and Mechanisms, 8 (9), p. 1105-19
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Keywords :
Angiogenesis; Focal adhesion; Integrin; Neuropilin-1; Tumour
Abstract :
[en] Anti-angiogenic treatments against alphavbeta3-integrin fail to block tumour growth in the long term, which suggests that the tumour vasculature escapes from angiogenesis inhibition through alphavbeta3-integrin-independent mechanisms. Here, we show that suppression of beta3-integrin in mice leads to the activation of a neuropilin-1 (NRP1)-dependent cell migration pathway in endothelial cells via a mechanism that depends on NRP1's mobilisation away from mature focal adhesions following VEGF-stimulation. The simultaneous genetic targeting of both molecules significantly impairs paxillin-1 activation and focal adhesion remodelling in endothelial cells, and therefore inhibits tumour angiogenesis and the growth of already established tumours. These findings provide a firm foundation for testing drugs against these molecules in combination to treat patients with advanced cancers.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Medical Translational Research (J. Schneider Group)
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Ellison, Tim S.
Atkinson, Samuel J.
Steri, Veronica
Kirkup, Benjamin M.
Preedy, Michael E. J.
Johnson, Robert T.
Ruhrberg, Christiana
Edwards, Dylan R.
Schneider, Jochen ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Weilbaecher, Katherine
Robinson, Stephen D.
External co-authors :
yes
Language :
English
Title :
Suppression of beta3-integrin in mice triggers a neuropilin-1-dependent change in focal adhesion remodelling that can be targeted to block pathological angiogenesis.
Publication date :
2015
Journal title :
Disease Models and Mechanisms
ISSN :
1754-8403
Publisher :
Company of Biologists, United Kingdom
Volume :
8
Issue :
9
Pages :
1105-19
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
(c) 2015. Published by The Company of Biologists Ltd.
Available on ORBilu :
since 16 May 2016

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