Role of PFKFB3-driven glycolysis in vessel sprouting

Katrien De Bock, Maria Georgiadou, Sandra Schoors, Anna Kuchnio, Brian W. Wong, Anna Rita Cantelmo, Annelies Quaegebeur, Bart Ghesquière, Sandra Cauwenberghs, Guy Eelen, Li Kun Phng, Inge Betz, Bieke Tembuyser, Katleen Brepoels, Jonathan Welti, Ilse Geudens, Inmaculada Segura, Bert Cruys, Franscesco Bifari, Ilaria DecimoRaquel Blanco, Sabine Wyns, Jeroen Vangindertael, Susana Rocha, Russel T. Collins, Sebastian Munck, Dirk Daelemans, Hiromi Imamura, Roland Devlieger, Mark Rider, Paul P. Van Veldhoven, Frans Schuit, Ramon Bartrons, Johan Hofkens, Peter Fraisl, Sucheta Telang, Ralph J. Deberardinis, Luc Schoonjans, Stefan Vinckier, Jason Chesney, Holger Gerhardt, Mieke Dewerchin, Peter Carmeliet

Research output: Contribution to journalArticle

524 Scopus citations

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.

Original languageEnglish
Pages (from-to)651-663
Number of pages13
JournalCell
Volume154
Issue number3
DOIs
StatePublished - Aug 1 2013
Externally publishedYes

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    De Bock, K., Georgiadou, M., Schoors, S., Kuchnio, A., Wong, B. W., Cantelmo, A. R., Quaegebeur, A., Ghesquière, B., Cauwenberghs, S., Eelen, G., Phng, L. K., Betz, I., Tembuyser, B., Brepoels, K., Welti, J., Geudens, I., Segura, I., Cruys, B., Bifari, F., ... Carmeliet, P. (2013). Role of PFKFB3-driven glycolysis in vessel sprouting. Cell, 154(3), 651-663. https://doi.org/10.1016/j.cell.2013.06.037