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Ellison, Tim S., Atkinson, Samuel J., Steri, Veronica, Kirkup, Benjamin M., Preedy, Michael E. J., Johnson, Robert T., 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 |
| UEA Research Groups: | Faculty of Science > Research Groups > Cells and Tissues Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies |
| Depositing User: | Pure Connector |
| Date Deposited: | 12 Nov 2015 16:00 |
| Last Modified: | 09 Mar 2024 00:51 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/55137 |
| DOI: | 10.1242/dmm.019927 |
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