Data di Pubblicazione:
2013
Citazione:
Role of PFKFB3-driven glycolysis in vessel sprouting / K. De Bock, M. Georgiadou, S. Schoors, A. Kuchnio, B.W. Wong, A.R. Cantelmo, A. Quaegebeur, B. Ghesquière, S. Cauwenberghs, G. Eelen, L. Phng, I. Betz, B. Tembuyser, K. Brepoels, J. Welti, I. Geudens, I. Segura, B. Cruys, F. Bifari, I. Decimo, R. Blanco, S. Wyns, J. Vangindertael, S. Rocha, R.T. Collins, S. Munck, D. Daelemans, H. Imamura, R. Devlieger, M. Rider, P.P. Van Veldhoven, F. Schuit, R. Bartrons, J. Hofkens, P. Fraisl, S. Telang, R.J. Deberardinis, L. Schoonjans, S. Vinckier, J. Chesney, H. Gerhardt, M. Dewerchin, P. Carmeliet. - In: CELL. - ISSN 0092-8674. - 154:3(2013 Aug 01), pp. 651-663. [10.1016/j.cell.2013.06.037]
Abstract:
Vessel sprouting by migrating tip and proliferating stalk endothelial cells (ECs) is controlled by genetic signals (such as Notch), but it is unknown whether metabolism also regulates this process. Here, we show that ECs relied on glycolysis rather than on oxidative phosphorylation for ATP production and that loss of the glycolytic activator PFKFB3 in ECs impaired vessel formation. Mechanistically, PFKFB3 not only regulated EC proliferation but also controlled the formation of filopodia/lamellipodia and directional migration, in part by compartmentalizing with F-actin in motile protrusions. Mosaic in vitro and in vivo sprouting assays further revealed that PFKFB3 overexpression overruled the pro-stalk activity of Notch, whereas PFKFB3 deficiency impaired tip cell formation upon Notch blockade, implying that glycolysis regulates vessel branching. © 2013 Elsevier Inc.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Animals; Cell Line, Tumor; Cells, Cultured; Endothelial Cells; Female; Gene Deletion; Gene Silencing; Humans; Male; Mice; Mice, Inbred C57BL; Phosphofructokinase-2; Pseudopodia; Zebrafish; Glycolysis; Neovascularization, Physiologic; Biochemistry, Genetics and Molecular Biology (all)
Elenco autori:
K. De Bock, M. Georgiadou, S. Schoors, A. Kuchnio, B.W. Wong, A.R. Cantelmo, A. Quaegebeur, B. Ghesquière, S. Cauwenberghs, G. Eelen, L. Phng, I. Betz, B. Tembuyser, K. Brepoels, J. Welti, I. Geudens, I. Segura, B. Cruys, F. Bifari, I. Decimo, R. Blanco, S. Wyns, J. Vangindertael, S. Rocha, R.T. Collins, S. Munck, D. Daelemans, H. Imamura, R. Devlieger, M. Rider, P.P. Van Veldhoven, F. Schuit, R. Bartrons, J. Hofkens, P. Fraisl, S. Telang, R.J. Deberardinis, L. Schoonjans, S. Vinckier, J. Chesney, H. Gerhardt, M. Dewerchin, P. Carmeliet
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