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Suppression of β3-integrin in mice triggers a neuropilin-1- dependent change in focal adhesion remodelling that can be targeted to block pathological angiogenesis

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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.

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Original languageEnglish
Pages (from-to)1105-1119
Number of pages15
JournalDisease Models & Mechanisms
Volume8
DOIs
StatePublished - 2015
Peer-reviewedYes

Keywords

    Research areas

  • Integrin, Neuropilin-1, Angiogenesis, Tumour, Focal adhesion

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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

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