Dissemin is shutting down on January 1st, 2025

Published in

The Company of Biologists, Disease Models and Mechanisms, 2015

DOI: 10.1242/dmm.019927

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

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Preprint: archiving allowed
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Postprint: archiving allowed
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Data provided by SHERPA/RoMEO

Abstract

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