Suppression of β3-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, Kirkup, Benjamin M., Preedy, Michael E. J., Johnson, Robert T. ORCID: https://orcid.org/0000-0003-3618-238X, Ruhrberg, Christiana, Edwards, Dylan R. ORCID: https://orcid.org/0000-0002-3292-2064, Schneider, Jochen G., Weilbaecher, Katherine and Robinson, Stephen D. ORCID: https://orcid.org/0000-0002-6606-7588 (2015) Suppression of β3-integrin in mice triggers a neuropilin-1- dependent change in focal adhesion remodelling that can be targeted to block pathological angiogenesis. Disease Models & Mechanisms, 8. pp. 1105-1119. ISSN 1754-8403

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Abstract

Anti-angiogenic treatments against αvβ3-integrin fail to block tumour growth in the long term, which suggests tumour vascular escape through αvβ3-integrin-independent mechanisms. Here, we show that suppression of β3-integrin 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.

Item Type:	Article
Additional Information:	This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed
Uncontrolled Keywords:	integrin,neuropilin-1,angiogenesis,tumour,focal adhesion,sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Science > School of Biological Sciences Faculty of Science
Depositing User:	Pure Connector
Date Deposited:	12 Nov 2015 16:00
Last Modified:	19 Apr 2023 02:31
URI:	https://ueaeprints.uea.ac.uk/id/eprint/55137
DOI:	10.1242/dmm.019927

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