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Role of PFKFB3-driven glycolysis in vessel sprouting

Item Type:Article
Title:Role of PFKFB3-driven glycolysis in vessel sprouting
Creators Name:De Bock, K. and Georgiadou, M. and Schoors, S. and Kuchnio, A. and Wong, B.W. and Cantelmo, A.R. and Quaegebeur, A. and Ghesquière, B. and Cauwenberghs, S. and Eelen, G. and Phng, L.K. and Betz, I. and Tembuyser, B. and Brepoels, K. and Welti, J. and Geudens, I. and Segura, I. and Cruys, B. and Bifari, F. and Decimo, I. and Blanco, R. and Wyns, S. and Vangindertael, J. and Rocha, S. and Collins, R.T. and Munck, S. and Daelemans, D. and Imamura, H. and Devlieger, R. and Rider, M. and Van Veldhoven, P.P. and Schuit, F. and Bartrons, R. and Hofkens, J. and Fraisl, P. and Telang, S. and DeBerardinis, R.J. and Schoonjans, L. and Vinckier, S. and Chesney, J. and Gerhardt, H. and Dewerchin, M. and Carmeliet, P.
Abstract:Vessel sprouting by migrating tip and proliferating stalk endothelial cells (ECs) is controlled by genetic signals (such as Notch), but it is unknown whether metabolism also regulates this process. Here, we show that ECs relied on glycolysis rather than on oxidative phosphorylation for ATP production and that loss of the glycolytic activator PFKFB3 in ECs impaired vessel formation. Mechanistically, PFKFB3 not only regulated EC proliferation but also controlled the formation of filopodia/lamellipodia and directional migration, in part by compartmentalizing with F-actin in motile protrusions. Mosaic in vitro and in vivo sprouting assays further revealed that PFKFB3 overexpression overruled the pro-stalk activity of Notch, whereas PFKFB3 deficiency impaired tip cell formation upon Notch blockade, implying that glycolysis regulates vessel branching.
Keywords:Cultured Cells, Endothelial Cells, Gene Deletion, Gene Silencing, Glycolysis, Inbred C57BL Mice, Phosphofructokinase-2, Physiologic Neovascularization, Pseudopodia, Tumor Cell Line, Animals, Mice, Zebrafish
Source:Cell
ISSN:0092-8674
Publisher:Cell Press (U.S.A.)
Volume:154
Number:3
Page Range:651-663
Date:1 August 2013
Official Publication:https://doi.org/10.1016/j.cell.2013.06.037
PubMed:View item in PubMed

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