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

446 Citations (Scopus)

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

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Endothelial cells
Glycolysis
Endothelial Cells
Pseudopodia
Oxidative Phosphorylation
Cell proliferation
Metabolism
Actins
Assays
Adenosine Triphosphate
Cell Proliferation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

De Bock, K., Georgiadou, M., Schoors, S., Kuchnio, A., Wong, B. W., Cantelmo, A. R., ... 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

Role of PFKFB3-driven glycolysis in vessel sprouting. / 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.

In: Cell, Vol. 154, No. 3, 01.08.2013, p. 651-663.

Research output: Contribution to journalArticle

De Bock, K, Georgiadou, M, Schoors, S, Kuchnio, A, Wong, BW, Cantelmo, AR, Quaegebeur, A, Ghesquière, B, Cauwenberghs, S, Eelen, G, Phng, LK, Betz, I, Tembuyser, B, Brepoels, K, Welti, J, Geudens, I, Segura, I, Cruys, B, Bifari, F, Decimo, I, Blanco, R, Wyns, S, Vangindertael, J, Rocha, S, Collins, RT, Munck, S, Daelemans, D, Imamura, H, Devlieger, R, Rider, M, Van Veldhoven, PP, Schuit, F, Bartrons, R, Hofkens, J, Fraisl, P, Telang, S, Deberardinis, RJ, Schoonjans, L, Vinckier, S, Chesney, J, Gerhardt, H, Dewerchin, M & Carmeliet, P 2013, 'Role of PFKFB3-driven glycolysis in vessel sprouting', Cell, vol. 154, no. 3, pp. 651-663. https://doi.org/10.1016/j.cell.2013.06.037
De Bock K, Georgiadou M, Schoors S, Kuchnio A, Wong BW, Cantelmo AR et al. Role of PFKFB3-driven glycolysis in vessel sprouting. Cell. 2013 Aug 1;154(3):651-663. https://doi.org/10.1016/j.cell.2013.06.037
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. / Role of PFKFB3-driven glycolysis in vessel sprouting. In: Cell. 2013 ; Vol. 154, No. 3. pp. 651-663.
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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.",
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AU - Schoors, Sandra

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AU - Wong, Brian W.

AU - Cantelmo, Anna Rita

AU - Quaegebeur, Annelies

AU - Ghesquière, Bart

AU - Cauwenberghs, Sandra

AU - Eelen, Guy

AU - Phng, Li Kun

AU - Betz, Inge

AU - Tembuyser, Bieke

AU - Brepoels, Katleen

AU - Welti, Jonathan

AU - Geudens, Ilse

AU - Segura, Inmaculada

AU - Cruys, Bert

AU - Bifari, Franscesco

AU - Decimo, Ilaria

AU - Blanco, Raquel

AU - Wyns, Sabine

AU - Vangindertael, Jeroen

AU - Rocha, Susana

AU - Collins, Russel T.

AU - Munck, Sebastian

AU - Daelemans, Dirk

AU - Imamura, Hiromi

AU - Devlieger, Roland

AU - Rider, Mark

AU - Van Veldhoven, Paul P.

AU - Schuit, Frans

AU - Bartrons, Ramon

AU - Hofkens, Johan

AU - Fraisl, Peter

AU - Telang, Sucheta

AU - Deberardinis, Ralph J.

AU - Schoonjans, Luc

AU - Vinckier, Stefan

AU - Chesney, Jason

AU - Gerhardt, Holger

AU - Dewerchin, Mieke

AU - Carmeliet, Peter

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