Journal
CELL METABOLISM
Volume 19, Issue 1, Pages 37-48Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2013.11.008
Keywords
-
Categories
Funding
- Flemish Association against Cancer (VLK)
- Institution of Research and Innovation (IWT)
- Federal Government Belgium grant [IUAP7/03]
- Flemish Government, a Concerted Research Activities Belgium grant [GOA2006/11]
- FWO [G.0532.10, G.0817.11, G.0834.13, 1.5.202.10N, G.0764.10N, 1.5.142.13N, G.0598.12]
- Foundation Leducq Transatlantic Network (ARTEMIS)
- Foundation against Cancer
- ERC [EU-ERC269073]
- Spanish Government
- European Union FEDER funds [SAF2011-25726]
- Generalitat de Catalunya-AGAUR [2009SGR1308]
- ICREA Academia prize
Ask authors/readers for more resources
Strategies targeting pathological angiogenesis have focused primarily on blocking vascular endothelial growth factor (VEGF), but resistance and insufficient efficacy limit their success, mandating alternative antiangiogenic strategies. We recently provided genetic evidence that the glycolytic activator phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) promotes vessel formation but did not explore the antiangiogenic therapeutic potential of PFKFB3 blockade. Here, we show that blockade of PFKFB3 by the small molecule 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) reduced vessel sprouting in endothelial cell (EC) spheroids, zebrafish embryos, and the postnatal mouse retina by inhibiting EC proliferation and migration. 3PO also suppressed vascular hyperbranching induced by inhibition of Notch or VEGF receptor 1 (VEGFR1) and amplified the antiangiogenic effect of VEGF blockade. Although 3PO reduced glycolysis only partially and transiently in vivo, this sufficed to decrease pathological neovascularization in ocular and inflammatory models. These insights may offer therapeutic antiangiogenic opportunities.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available