Reference : Suppression of beta3-integrin in mice triggers a neuropilin-1-dependent change in foc...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Suppression 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 [> >]
Kirkup, Benjamin M. [> >]
Preedy, Michael E. J. [> >]
Johnson, Robert T. [> >]
Ruhrberg, Christiana [> >]
Edwards, Dylan R. [> >]
Schneider, Jochen mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Weilbaecher, Katherine [> >]
Robinson, Stephen D. [> >]
Disease Models and Mechanisms
Yes (verified by ORBilu)
[en] Angiogenesis ; Focal adhesion ; Integrin ; Neuropilin-1 ; Tumour
[en] 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.
Luxembourg Centre for Systems Biomedicine (LCSB): Medical Translational Research (J. Schneider Group)
(c) 2015. Published by The Company of Biologists Ltd.

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