Universität zu Köln

Delaunay, Sylvain, Rapino, Francesca ORCID: 0000-0002-4343-3805, Tharun, Lars, Zhou, Zhaoli, Heukamp, Lukas ORCID: 0000-0002-3388-3482, Termathe, Martin ORCID: 0000-0002-5618-4633, Shostak, Kateryna, Klevernic, Iva, Florin, Alexandra, Desmecht, Hadrien, Desmet, Christophe J., Nguyen, Laurent ORCID: 0000-0002-8560-3008, Leidel, Sebastian A., Willis, Anne E., Buettner, Reinhard, Chariot, Alain and Close, Pierre (2016). Elp3 links tRNA modification to IRES-dependent translation of LEF1 to sustain metastasis in breast cancer. J. Exp. Med., 213 (11). S. 2503 - 2524. NEW YORK: ROCKEFELLER UNIV PRESS. ISSN 1540-9538

Full text not available from this repository.

Abstract

Quantitative and qualitative changes in mRNA translation occur in tumor cells and support cancer progression and metastasis. Posttranscriptional modifications of transfer RNAs (tRNAs) at the wobble uridine 34 (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 up-regulated 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 proinvasive 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 that the key role of U34 tRNA modification is 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Delaunay, Sylvain UNSPECIFIED UNSPECIFIED UNSPECIFIED Rapino, Francesca UNSPECIFIED orcid.org/0000-0002-4343-3805 UNSPECIFIED Tharun, Lars UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhou, Zhaoli UNSPECIFIED UNSPECIFIED UNSPECIFIED Heukamp, Lukas UNSPECIFIED orcid.org/0000-0002-3388-3482 UNSPECIFIED Termathe, Martin UNSPECIFIED orcid.org/0000-0002-5618-4633 UNSPECIFIED Shostak, Kateryna UNSPECIFIED UNSPECIFIED UNSPECIFIED Klevernic, Iva UNSPECIFIED UNSPECIFIED UNSPECIFIED Florin, Alexandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Desmecht, Hadrien UNSPECIFIED UNSPECIFIED UNSPECIFIED Desmet, Christophe J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nguyen, Laurent UNSPECIFIED orcid.org/0000-0002-8560-3008 UNSPECIFIED Leidel, Sebastian A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Willis, Anne E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Chariot, Alain UNSPECIFIED UNSPECIFIED UNSPECIFIED Close, Pierre UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-261612
DOI:	10.1084/jem.20160397
Journal or Publication Title:	J. Exp. Med.
Volume:	213
Number:	11
Page Range:	S. 2503 - 2524
Date:	2016
Publisher:	ROCKEFELLER UNIV PRESS
Place of Publication:	NEW YORK
ISSN:	1540-9538
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EPITHELIAL-MESENCHYMAL TRANSFORMATION; GENE-EXPRESSION; FAMILIAL DYSAUTONOMIA; THIO-MODIFICATION; TUMOR INITIATION; WOBBLE POSITION; CELL-MIGRATION; MODIFIER URM1; DEK ONCOGENE; WNT PATHWAY Multiple languages Immunology; Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26161