Article (Scientific journals)
Impaired angiogenesis and tumor development by inhibition of the mitotic kinesin Eg5.
Exertier, Prisca; Javerzat, Sophie; Wang, Baigang et al.
2013In Oncotarget, 4 (12), p. 2302-16
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Keywords :
cancer; kinesin; angiogenesis
Abstract :
[en] Kinesin motor proteins exert essential cellular functions in all eukaryotes. They control mitosis, migration and intracellular transport through interaction with microtubules. Small molecule inhibitors of the mitotic kinesin KiF11/Eg5 are a promising new class of anti-neoplastic agents currently evaluated in clinical cancer trials for solid tumors and hematological malignancies. Here we report induction of Eg5 and four other mitotic kinesins including KIF20A/Mklp2 upon stimulation of in vivo angiogenesis with vascular endothelial growth factor-A (VEGF-A). Expression analyses indicate up-regulation of several kinesin-encoding genes predominantly in lymphoblasts and endothelial cells. Chemical blockade of Eg5 inhibits endothelial cell proliferation and migration in vitro. Mitosis-independent vascular outgrowth in aortic ring cultures is strongly impaired after Eg5 or Mklp2 protein inhibition. In vivo, interfering with KIF11/Eg5 function causes developmental and vascular defects in zebrafish and chick embryos and potent inhibition of tumor angiogenesis in experimental tumor models. Besides blocking tumor cell proliferation, impairing endothelial function is a novel mechanism of action of kinesin inhibitors.
Disciplines :
Oncology
Author, co-author :
Exertier, Prisca
Javerzat, Sophie
Wang, Baigang
Franco, Melanie
Herbert, John
Platonova, Natalia
Winandy, Marie  ;  Université de Liège - ULiège > GIGA-Management : Plate-forme zebrafish
Pujol, Nadege
Nivelles, Olivier
Ormenese, Sandra ;  Université de Liège - ULiège > GIGA-Management : Pl-forme imagerie cell. et cytom. de flux
Godard, Virginie
Becker, Jurgen
Bicknell, Roy
Pineau, Raphael
Wilting, Jorg
Bikfalvi, Andreas
Hagedorn, Martin
More authors (7 more) Less
Language :
English
Title :
Impaired angiogenesis and tumor development by inhibition of the mitotic kinesin Eg5.
Publication date :
2013
Journal title :
Oncotarget
eISSN :
1949-2553
Publisher :
Impact Journals, United States - New York
Volume :
4
Issue :
12
Pages :
2302-16
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 19 February 2014

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