Elp3 links tRNA modification to IRES-dependent translation of LEF1 to sustain metastasis in breast cancer.

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 DE

SUBMITTER: Delaunay S 

PROVIDER: S-EPMC5068235 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature