No full text
Scientific conference in universities or research centers (Scientific conferences in universities or research centers)
Elongator: mcm5s2 modification fosters breast cancer metastasis
Delaunay, Sylvain; Rapino, Francesca; Zhou, Zhaoli et al.
2015
 

Files


Full Text
No document available.

Send to



Details



Keywords :
Elongator; Metastasis; Breast
Abstract :
[en] Quantitative and qualitative changes in mRNA translation occur in tumor cells and support cancer progression and metastasis. Post-transcriptional nucleoside modifications of transfer RNAs (tRNAs) at the wobble U34 base are highly conserved and contribute to translation fidelity. Here, we show that ELP3 and CTU1/2, partner enzymes in U34 mcm5s2-tRNA modification, are upregulated in human breast cancers and sustain metastasis. Elp3 genetic ablation strongly impaired invasion and metastasis formation in the PyMT model of invasive breast cancer. Mechanistically, ELP3 and CTU1/2 support cellular invasion through the translation of the oncoprotein DEK. As a result, DEK promotes the IRES-dependent translation of the pro-invasive transcription factor LEF1. Consistently, a DEK mutant, whose codon composition is independent of U34 mcm5s2-tRNA modification, escapes the ELP3- and CTU1- dependent regulation and restores the IRES-dependent LEF1 expression. Our results demonstrate the key role of U34 tRNA modification to support specific translation during breast cancer progression and highlight a functional link between tRNA modification- and IRES-dependent translation during tumor cell invasion and metastasis.
Research center :
Giga-Signal Transduction - ULiège
Disciplines :
Oncology
Author, co-author :
Delaunay, Sylvain ;  Université de Liège > Département de pharmacie > Chimie médicale
Rapino, Francesca  ;  Université de Liège > Département de pharmacie > Chimie médicale
Zhou, Zhaoli ;  Université de Liège > Département de pharmacie > Chimie médicale
LADANG, Aurélie  ;  Centre Hospitalier Universitaire de Liège - CHU > Frais communs Biologie clinique - Pool assistants
Shostak, Kateryna ;  Université de Liège > Département de pharmacie > Chimie médicale
Chariot, Alain ;  Université de Liège > Département de pharmacie > Chimie médicale
Close, Pierre  ;  Université de Liège > Département de pharmacie > Chimie médicale
Language :
English
Title :
Elongator: mcm5s2 modification fosters breast cancer metastasis
Alternative titles :
[en] Elongator: la modification mcm5s2 promeut la formation de métastases dans le cancer du sein
Publication date :
09 March 2015
Number of pages :
30
Event name :
MRC toxicology meeting
Event organizer :
Anne E Willis
Event place :
Leicester, United Kingdom
Event date :
Le 9 mars 2015
Name of the research project :
Insight into the role of Elongator in breast cancer
Funders :
ULiège - Université de Liège [BE]
Available on ORBi :
since 30 August 2016

Statistics


Number of views
146 (13 by ULiège)
Number of downloads
0 (0 by ULiège)

Bibliography


Similar publications



Contact ORBi