Cell
Volume 154, Issue 3, 1 August 2013, Pages 651-663
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Article
Role of PFKFB3-Driven Glycolysis in Vessel Sprouting

https://doi.org/10.1016/j.cell.2013.06.037Get rights and content
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Highlights

  • Glycolysis is the major source of ATP production in endothelial cells

  • Silencing of the glycolytic regulator PFKFB3 impairs angiogenesis

  • PFKFB3-driven glycolysis overrules the pro-stalk activity of Notch

  • PFKFB3 regulates tip and stalk cell behavior and compartmentalizes with F-actin

Summary

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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These authors contributed equally to this work