Title: Role of PFKFB3-driven glycolysis in vessel sprouting
Authors: De Bock, Katrien *
Georgiadou, Maria *
Schoors, Sandra
Kuchnio, Anna
Wong, Brian W
Cantelmo, Anna Rita
Quaegebeur, Annelies
Ghesquière, Bart
Cauwenberghs, Sandra
Eelen, Guy
Phng, Li-Kun
Betz, Inge
Tembuyser, Bieke
Brepoels, Katleen
Welti, Jonathan
Geudens, Ilse
Segura, Inmaculada
Cruys, Bert
Bifari, Franscesco
Decimo, Ilaria
Blanco, Raquel
Wyns, Sabine
Vangindertael, Jeroen
Rocha, Susana
Collins, Russel T
Munck, Sebastian
Daelemans, Dirk
Imamura, Hiromi
Devlieger, Roland
Rider, Mark
Van Veldhoven, Paul P
Schuit, Frans
Bartrons, Ramon
Hofkens, Johan
Fraisl, Peter
Telang, Sucheta
Deberardinis, Ralph J
Schoonjans, Luc
Vinckier, Stefan
Chesney, Jason
Gerhardt, Holger
Dewerchin, Mieke
Carmeliet, Peter # ×
Issue Date: Aug-2013
Publisher: MIT Press
Series Title: Cell vol:154 issue:3 pages:651-663
Article number: 10.1016/j.cell.2013.06.037
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.
ISSN: 0092-8674
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
Laboratory of Angiogenesis and Vascular Metabolism (VIB-KU Leuven Centre for Cancer Biology) (+)
* (joint) first author
× corresponding author
# (joint) last author

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