Role of PFKFB3-Driven Glycolysis in Vessel Sprouting

被引：1219

作者：

De Bock, Katrien ^{[1
,10
]}

Georgiadou, Maria ^{[1
,10
]}

Schoors, Sandra ^{[1
,10
]}

Kuchnio, Anna ^{[1
,10
]}

Wong, Brian W. ^{[1
,10
]}

Cantelmo, Anna Rita ^{[1
,10
]}

Quaegebeur, Annelies ^{[1
,10
]}

Ghesquiere, Bart ^{[1
,10
]}

Cauwenberghs, Sandra ^{[1
,10
]}

Eelen, Guy ^{[1
,10
]}

Phng, Li-Kun ^{[2
,11
]}

Betz, Inge ^{[1
,10
]}

Tembuyser, Bieke ^{[1
,10
]}

Brepoels, Katleen ^{[1
,10
]}

Welti, Jonathan ^{[1
,10
]}

Geudens, Ilse ^{[2
,11
]}

Segura, Inmaculada ^{[1
,10
]}

Cruys, Bert ^{[1
,10
]}

Bifari, Franscesco ^{[1
,10
]}

Decimo, Ilaria ^{[1
,10
]}

Blanco, Raquel ^{[14
]}

Wyns, Sabine ^{[1
,10
]}

Vangindertael, Jeroen ^{[3
]}

Rocha, Susana ^{[3
]}

Collins, Russel T. ^{[14
]}

Munck, Sebastian ^{[4
,12
]}

Daelemans, Dirk ^{[5
]}

Imamura, Hiromi ^{[15
,16
]}

Devlieger, Roland ^{[6
]}

Rider, Mark ^{[17
]}

Van Veldhoven, Paul P. ^{[7
]}

Schuit, Frans ^{[8
]}

Bartrons, Ramon ^{[18
]}

Hofkens, Johan ^{[3
]}

Fraisl, Peter ^{[1
,9
,10
,13
]}

Telang, Sucheta ^{[19
]}

DeBerardinis, Ralph J. ^{[20
]}

Schoonjans, Luc ^{[1
,10
]}

Vinckier, Stefan ^{[1
,10
]}

Chesney, Jason ^{[19
]}

Gerhardt, Holger ^{[2
,11
,14
]}

Dewerchin, Mieke ^{[1
,10
]}

Carmeliet, Peter ^{[1
,10
]}

机构：

[1] Univ Louvain, Vesalius Res Ctr, Lab Angiogenesis & Neurovasc Link, Dept Oncol, B-3000 Louvain, Belgium

[2] Univ Louvain, Vesalius Res Ctr, Vasc Patterning Lab, Dept Oncol, B-3000 Louvain, Belgium

[3] Univ Louvain, Mol Imaging & Photon Lab, B-3000 Louvain, Belgium

[4] Univ Louvain, Ctr Human Genet, B-3000 Louvain, Belgium

[5] Univ Louvain, Rega Inst, Lab Virol & Chemotherapy, B-3000 Louvain, Belgium

[6] Univ Louvain, Dept Gynaecol & Obstet, B-3000 Louvain, Belgium

[7] Univ Louvain, Lab Lipid Biochem & Prot Interact, B-3000 Louvain, Belgium

[8] Univ Louvain, Gene Express Unit, B-3000 Louvain, Belgium

[9] Univ Louvain, Vesalius Res Ctr, Dept Oncol, Lab Cell Proliferat, B-3000 Louvain, Belgium

[10] VIB, Vesalius Res Ctr, Lab Angiogenesis & Neurovasc Link, B-3000 Louvain, Belgium

[11] VIB, Vesalius Res Ctr, Vasc Patterning Lab, B-3000 Louvain, Belgium

[12] VIB, Ctr Biol Dis, B-3000 Louvain, Belgium

[13] VIB, Vesalius Res Ctr, Lab Cell Proliferat, B-3000 Louvain, Belgium

[14] Canc Res UK, London Res Inst, Vasc Biol Lab, London WC2A 3LY, England

[15] Kyoto Univ, Hakubi Ctr Adv Res, Kyoto 6068501, Japan

[16] Kyoto Univ, Grad Sch Biostudies, Kyoto 6068501, Japan

[17] Univ Louvain, De Duve Inst, Hormone & Prot Phosphorylat Res Lab, B-1200 Brussels, Belgium

[18] Univ Barcelona, IDIBELL, Dept Ciencies Fisiol 2, Barcelona 08907, Spain

[19] Univ Louisville, James Graham Brown Canc Ctr, Louisville, KY 40202 USA

[20] Univ Texas SW Med Ctr Dallas, Childrens Med Ctr Res Inst, Dallas, TX 75390 USA

来源：

CELL | 2013年 / 154卷 / 03期

基金：

欧洲研究理事会;

关键词：

CORONARY ENDOTHELIAL-CELLS; AEROBIC GLYCOLYSIS; CANCER; 6-PHOSPHOFRUCTO-2-KINASE; METABOLISM; ENERGY; REQUIRES; MODEL; NOTCH;

D O I：

10.1016/j.cell.2013.06.037

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：651 / 663

页数：13

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