Glycolytic regulation of cell rearrangement in angiogenesis
| Autor: | Saar Vandekeere, Brian W. Wong, Stefan Vinckier, Elisabetta Dejana, Peter Carmeliet, Holger Gerhardt, Anna Rita Cantelmo, Anna Kuchnio, Lena Christin Conradi, Ann Bouché, Mieke Dewerchin, Roeland M. H. Merks, Katie Bentley, Bert Cruys, Ivo Cornelissen, Dries Verdegem |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Vascular Endothelial Growth Factor A
0301 basic medicine Medicin och hälsovetenskap Indoles Phosphofructokinase-2 Pyridines Angiogenesis Science Cell Neovascularization Physiologic General Physics and Astronomy Biology Models Biological Medical and Health Sciences Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Adenosine Triphosphate Antigens CD Human Umbilical Vein Endothelial Cells medicine Humans Computer Simulation Pyrroles Glycolysis Pseudopodia Cytoskeleton Multidisciplinary Activator (genetics) General Chemistry Cadherins Cell biology Vascular endothelial growth factor A 030104 developmental biology medicine.anatomical_structure Cardiovascular and Metabolic Diseases Gene Knockdown Techniques cardiovascular system Intracellular |
| Zdroj: | Nature Communications Nature Communications, 7 Nature Communications, Vol 7, Iss 1, Pp 1-15 (2016) Cruys, B, Wong, B W, Kuchnio, A, Verdegem, D, Cantelmo, A R, Conradi, L C, Vandekeere, S, Bouche, A, Cornelissen, I, Vinckier, S, Merks, R M H, Dejana, E, Gerhardt, H, Dewerchin, M, Bentley, K & Carmeliet, P 2016, ' Glycolytic regulation of cell rearrangement in angiogenesis ', Nature Communications, vol. 7, 12240, pp. 1-15 . https://doi.org/10.1038/ncomms12240 Nature Communications, 7, 12240. Nature Research |
| ISSN: | 2041-1723 |
| Popis: | 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. Glycolytic regulator PFKFB3 is a key player in vessel sprouting. Here the authors develop a computational model predicting that PFKFB3 drives endothelial cell rearrangement during vessel sprouting by promoting filopodia formation and reducing intercellular adhesion, and empirically validate this prediction. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|