Reference : Elongator: mcm5s2 modification fosters breast cancer metastasis
Scientific conferences in universities or research centers : Scientific conference in universities or research centers
Human health sciences : Oncology
http://hdl.handle.net/2268/201310
Elongator: mcm5s2 modification fosters breast cancer metastasis
English
[en] Elongator: la modification mcm5s2 promeut la formation de métastases dans le cancer du sein
Delaunay, Sylvain mailto [Université de Liège > Département de pharmacie > Chimie médicale >]
Rapino, Francesca mailto [Université de Liège > Département de pharmacie > Chimie médicale >]
Zhou, Zhaoli mailto [Université de Liège > Département de pharmacie > Chimie médicale >]
LADANG, Aurélie mailto [Centre Hospitalier Universitaire de Liège - CHU > > Frais communs Biologie clinique - Pool assistants >]
Shostak, Kateryna mailto [Université de Liège > Département de pharmacie > Chimie médicale >]
Chariot, Alain mailto [Université de Liège > Département de pharmacie > Chimie médicale >]
Close, Pierre mailto [Université de Liège > Département de pharmacie > Chimie médicale >]
9-Mar-2015
30
MRC toxicology meeting
Le 9 mars 2015
Anne E Willis
Leicester
Angleterre
[en] Elongator ; Metastasis ; Breast
[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.
Giga-Signal Transduction
Ulg
Insight into the role of Elongator in breast cancer
http://hdl.handle.net/2268/201310

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