TY - JOUR
T1 - Glycolytic regulation of cell rearrangement in angiogenesis
AU - Cruys, Bert
AU - Wong, Brian W.
AU - Kuchnio, Anna
AU - Verdegem, Dries
AU - Cantelmo, Anna Rita
AU - Conradi, Lena Christin
AU - Vandekeere, Saar
AU - Bouche, Ann
AU - Cornelissen, Ivo
AU - Vinckier, Stefan
AU - Merks, Roeland M.H.
AU - Dejana, Elisabetta
AU - Gerhardt, Holger
AU - Dewerchin, Mieke
AU - Bentley, Katie
AU - Carmeliet, Peter
N1 - Funding Information:
The work of M.D. is supported by a Foundation against Cancer grant (2012-177) and FWO (G.0699.15N); K.B. is funded by the Beth Israel Deaconess Medical Center (BIDMC) and the Knut and Alice Wallenberg Foundation. The work of P.C. is supported by a Belgium Science Policy grant (IUAP P7/03), long-term structural Methusalem funding by the Flemish Government, grants from FWO (G.0834.13N, G.0764.10N, G.0532.10N), the Foundation Leducq Transatlantic Network (grant ARTEMIS), Foundation against Cancer (2012-175),an ERC Advanced Research Grant (EU-ERC269073) and AXA Research Fund.
PY - 2016/7/20
Y1 - 2016/7/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84979523593&partnerID=8YFLogxK
U2 - 10.1038/ncomms12240
DO - 10.1038/ncomms12240
M3 - Article
C2 - 27436424
AN - SCOPUS:84979523593
SN - 2041-1723
VL - 7
JO - Nature communications
JF - Nature communications
M1 - 12240
ER -