title: Role of PFKFB3-driven glycolysis in vessel sprouting.
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.
authors.affiliation: Laboratory of Angiogenesis and Neurovascular Link, Vesalius Research Center, Department of Oncology, University of Leuven, Leuven 3000, Belgium.
authors.forename: Katrien
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authors.lastname: De Bock
authors.forename: Maria
authors.initials: M
authors.lastname: Georgiadou
authors.forename: Sandra
authors.initials: S
authors.lastname: Schoors
authors.forename: Anna
authors.initials: A
authors.lastname: Kuchnio
authors.forename: Brian W
authors.initials: BW
authors.lastname: Wong
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Cantelmo
authors.forename: Annelies
authors.initials: A
authors.lastname: Quaegebeur
authors.forename: Bart
authors.initials: B
authors.lastname: Ghesquière
authors.forename: Sandra
authors.initials: S
authors.lastname: Cauwenberghs
authors.forename: Guy
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authors.lastname: Eelen
authors.forename: Li-Kun
authors.initials: LK
authors.lastname: Phng
authors.forename: Inge
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authors.lastname: Betz
authors.forename: Bieke
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authors.lastname: Tembuyser
authors.forename: Katleen
authors.initials: K
authors.lastname: Brepoels
authors.forename: Jonathan
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authors.lastname: Welti
authors.forename: Ilse
authors.initials: I
authors.lastname: Geudens
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Segura
authors.forename: Bert
authors.initials: B
authors.lastname: Cruys
authors.forename: Franscesco
authors.initials: F
authors.lastname: Bifari
authors.forename: Ilaria
authors.initials: I
authors.lastname: Decimo
authors.forename: Raquel
authors.initials: R
authors.lastname: Blanco
authors.forename: Sabine
authors.initials: S
authors.lastname: Wyns
authors.forename: Jeroen
authors.initials: J
authors.lastname: Vangindertael
authors.forename: Susana
authors.initials: S
authors.lastname: Rocha
authors.forename: Russel T
authors.initials: RT
authors.lastname: Collins
authors.forename: Sebastian
authors.initials: S
authors.lastname: Munck
authors.forename: Dirk
authors.initials: D
authors.lastname: Daelemans
authors.forename: Hiromi
authors.initials: H
authors.lastname: Imamura
authors.forename: Roland
authors.initials: R
authors.lastname: Devlieger
authors.forename: Mark
authors.initials: M
authors.lastname: Rider
authors.forename: Paul P
authors.initials: PP
authors.lastname: Van Veldhoven
authors.forename: Frans
authors.initials: F
authors.lastname: Schuit
authors.forename: Ramon
authors.initials: R
authors.lastname: Bartrons
authors.forename: Johan
authors.initials: J
authors.lastname: Hofkens
authors.forename: Peter
authors.initials: P
authors.lastname: Fraisl
authors.forename: Sucheta
authors.initials: S
authors.lastname: Telang
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Deberardinis
authors.forename: Luc
authors.initials: L
authors.lastname: Schoonjans
authors.forename: Stefan
authors.initials: S
authors.lastname: Vinckier
authors.forename: Jason
authors.initials: J
authors.lastname: Chesney
authors.forename: Holger
authors.initials: H
authors.lastname: Gerhardt
authors.forename: Mieke
authors.initials: M
authors.lastname: Dewerchin
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D020868:Gene Silencing; D006019:Glycolysis; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D025481:Phosphofructokinase-2 / Q000235:genetics / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism; D015027:Zebrafish
chemical_list: C107345:PFKFB3 protein, human; D025481:Phosphofructokinase-2