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| Item Type: | Article |
|---|---|
| Title: | Glycolytic regulation of cell rearrangement in angiogenesis |
| Creators Name: | Cruys, B., Wong, B.W., Kuchnio, A., Verdegem, D., Cantelmo, A. R., Conradi, L.C., Vandekeere, S., Bouché, A., Cornelissen, I., Vinckier, S., Merks, R.M.H., Dejana, E., Gerhardt, H., Dewerchin, M., Bentley, K. and Carmeliet, P. |
| Abstract: | 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. |
| Keywords: | Adenosine Triphosphate, CD, Antigens, Cadherins, Computer Simulation, Gene Knockdown Techniques, Glycolysis, Human Umbilical Vein Endothelial Cells, Indoles, Biological, Models, Physiologic, Neovascularization, Phosphofructokinase-2, Pseudopodia, Pyridines, Vascular Endothelial Growth Factor A |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 7 |
| Page Range: | 12240 |
| Date: | 20 July 2016 |
| Official Publication: | https://doi.org/10.1038/ncomms12240 |
| PubMed: | View item in PubMed |
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