Journal
NATURE COMMUNICATIONS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms12240
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Funding
- Hercules Foundation
- Flemish Government-Department EWI
- Agency for Innovation by Science and Technology in Flanders (IWT)
- Research Foundation Flanders (FWO)
- Marie Curie Incoming International fellowship
- FWO
- Emmanuel van der Schueren funding of the Vlaamse Liga tegen Kanker
- Else Kroner-Fresenius-Stiftung
- Division for Earth and Life Sciences (ALW)
- Netherlands Organization for Scientific Research (NWO)
- Italian Association for Cancer Research [IG14471]
- Cancer Research UK
- Foundation Leducq Transatlantic Network (grant ARTEMIS)
- Lister Institute of Preventive Medicine
- European Research Council (ERC) Starting Grant [EU-ERC311719]
- Foundation against Cancer grant [2012-177]
- FWO [G.0699.15N, G.0834.13N, G.0764.10N, G.0532.10N]
- Beth Israel Deaconess Medical Center (BIDMC)
- Knut and Alice Wallenberg Foundation
- Belgium Science Policy grant [IUAP P7/03]
- long-term structural Methusalem - Flemish Government
- Foundation against Cancer [2012-175]
- ERC Advanced Research Grant [EU-ERC269073]
- AXA Research Fund
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During vessel sprouting, endothelial cells (ECs) dynamically rearrange positions in the sprout to compete for the tip position. We recently identified a key role for the glycolytic activator PFKFB3 in vessel sprouting by regulating cytoskeleton remodelling, migration and tip cell competitiveness. It is, however, unknown how glycolysis regulates EC rearrangement during vessel sprouting. Here we report that computational simulations, validated by experimentation, predict that glycolytic production of ATP drives EC rearrangement by promoting filopodia formation and reducing intercellular adhesion. Notably, the simulations correctly predicted that blocking PFKFB3 normalizes the disturbed EC rearrangement in high VEGF conditions, as occurs during pathological angiogenesis. This interdisciplinary study integrates EC metabolism in vessel sprouting, yielding mechanistic insight in the control of vessel sprouting by glycolysis, and suggesting anti-glycolytic therapy for vessel normalization in cancer and non-malignant diseases.
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