Article (Scientific journals)
Nucleolin Promotes Heat Shock-Associated Translation of VEGF-D to Promote Tumor Lymphangiogenesis.
Morfoisse, Florent; Tatin, Florence; Hantelys, Fransky et al.
2016In Cancer Research, 76 (15), p. 4394-405
Peer Reviewed verified by ORBi
 

Files


Full Text
Cancer Research FM 2016.pdf
Publisher postprint (1.91 MB)
Download

All documents in ORBi are protected by a user license.

Send to



Details



Abstract :
[en] The vascular endothelial growth factor VEGF-D promotes metastasis by inducing lymphangiogenesis and dilatation of the lymphatic vasculature, facilitating tumor cell extravasion. Here we report a novel level of control for VEGF-D expression at the level of protein translation. In human tumor cells, VEGF-D colocalized with eIF4GI and 4E-BP1, which can program increased initiation at IRES motifs on mRNA by the translational initiation complex. In murine tumors, the steady-state level of VEGF-D protein was increased despite the overexpression and dephosphorylation of 4E-BP1, which downregulates protein synthesis, suggesting the presence of an internal ribosome entry site (IRES) in the 5' UTR of VEGF-D mRNA. We found that nucleolin, a nucleolar protein involved in ribosomal maturation, bound directly to the 5'UTR of VEGF-D mRNA, thereby improving its translation following heat shock stress via IRES activation. Nucleolin blockade by RNAi-mediated silencing or pharmacologic inhibition reduced VEGF-D translation along with a subsequent constriction of lymphatic vessels in tumors. Our results identify nucleolin as a key regulator of VEGF-D expression, deepening understanding of lymphangiogenesis control during tumor formation. Cancer Res; 76(15); 4394-405. (c)2016 AACR.
Disciplines :
Biotechnology
Author, co-author :
Morfoisse, Florent ;  Université de Liège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Tatin, Florence
Hantelys, Fransky
Adoue, Aurelien
Helfer, Anne-Catherine
Cassant-Sourdy, Stephanie
Pujol, Francoise
Gomez-Brouchet, Anne
Ligat, Laetitia
Lopez, Frederic
Pyronnet, Stephane
Courty, Jose
Guillermet-Guibert, Julie
Marzi, Stefano
Schneider, Robert J.
Prats, Anne-Catherine
Garmy-Susini, Barbara H.
More authors (7 more) Less
Language :
English
Title :
Nucleolin Promotes Heat Shock-Associated Translation of VEGF-D to Promote Tumor Lymphangiogenesis.
Publication date :
01 August 2016
Journal title :
Cancer Research
ISSN :
0008-5472
eISSN :
1538-7445
Publisher :
American Association for Cancer Research, United States - Maryland
Volume :
76
Issue :
15
Pages :
4394-405
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
(c)2016 American Association for Cancer Research.
Available on ORBi :
since 02 June 2017

Statistics


Number of views
75 (2 by ULiège)
Number of downloads
230 (0 by ULiège)

Scopus citations®
 
21
Scopus citations®
without self-citations
14
OpenCitations
 
21

Bibliography


Similar publications



Contact ORBi