Suppression of β3-integrin in mice triggers a neuropilin-1-dependent change in focal adhesion remodelling that can be targeted to block pathological angiogenesis
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 o...
Main Authors: | , , , , , , , , , , |
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Format: | Article |
Language: | English |
Published: |
The Company of Biologists
2015-09-01
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Series: | Disease Models & Mechanisms |
Subjects: | |
Online Access: | http://dmm.biologists.org/content/8/9/1105 |
Summary: | 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. |
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ISSN: | 1754-8411 1754-8403 |