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See detailSuppression of beta3-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 et al

in Disease Models and Mechanisms (2015), 8(9), 1105-19

Anti-angiogenic treatments against alphavbeta3-integrin fail to block tumour growth in the long term, which suggests that the tumour vasculature escapes from angiogenesis inhibition through alphavbeta3 ... [more ▼]

Anti-angiogenic treatments against alphavbeta3-integrin fail to block tumour growth in the long term, which suggests that the tumour vasculature escapes from angiogenesis inhibition through alphavbeta3-integrin-independent mechanisms. Here, we show that suppression of beta3-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. [less ▲]

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