Glycolytic regulation of cell rearrangement in angiogenesis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-07-20

AUTHORS

Bert Cruys, Brian W. Wong, Anna Kuchnio, Dries Verdegem, Anna Rita Cantelmo, Lena-Christin Conradi, Saar Vandekeere, Ann Bouché, Ivo Cornelissen, Stefan Vinckier, Roeland M. H. Merks, Elisabetta Dejana, Holger Gerhardt, Mieke Dewerchin, Katie Bentley, Peter Carmeliet

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. More... »

PAGES

12240

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms12240

DOI

http://dx.doi.org/10.1038/ncomms12240

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1042504348

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27436424


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