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Glycolytic regulation of cell rearrangement in angiogenesis

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Official URL:https://doi.org/10.1038/ncomms12240
PubMed:View item in PubMed
Creators Name:Cruys, B. and Wong, B.W. and Kuchnio, A. and Verdegem, D. and Cantelmo, A. R. and Conradi, L.C. and Vandekeere, S. and Bouche, A. and Cornelissen, I. and Vinckier, S. and Merks, R.M.H. and Dejana, E. and Gerhardt, H. and Dewerchin, M. and Bentley, K. and Carmeliet, P.
Journal Title:Nature Communications
Journal Abbreviation:Nat Commun
Volume:7
Page Range:12240
Date:20 July 2016
Abstract:During vessel sprouting, endothelial cells (ECs) dynamically rearrange positions in the sprout to compete for the tip position. We recently identified a key role for the glycolytic activator PFKFB3 in vessel sprouting by regulating cytoskeleton remodelling, migration and tip cell competitiveness. It is, however, unknown how glycolysis regulates EC rearrangement during vessel sprouting. Here we report that computational simulations, validated by experimentation, predict that glycolytic production of ATP drives EC rearrangement by promoting filopodia formation and reducing intercellular adhesion. Notably, the simulations correctly predicted that blocking PFKFB3 normalizes the disturbed EC rearrangement in high VEGF conditions, as occurs during pathological angiogenesis. This interdisciplinary study integrates EC metabolism in vessel sprouting, yielding mechanistic insight in the control of vessel sprouting by glycolysis, and suggesting anti-glycolytic therapy for vessel normalization in cancer and non-malignant diseases.
ISSN:2041-1723
Publisher:Nature Publishing Group (U.K.)
Item Type:Article

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