LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression..pdf (3.23 MB)
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LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression

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journal contribution
posted on 23.02.2016, 12:19 by M. Mura, T. G. Hopkins, T. Michael, N. Abd-Latip, J. Weir, E. Aboagye, F. Mauri, C. Jameson, J. Sturge, H. Gabra, Martin David Bushell, A. E. Willis, E. Curry, S. P. Blagden
RNA-binding proteins (RBPs) bind to and post-transcriptionally regulate the stability of mRNAs. La-related protein 1 (LARP1) is a conserved RBP that interacts with poly-A-binding protein and is known to regulate 5'-terminal oligopyrimidine tract (TOP) mRNA translation. Here, we show that LARP1 is complexed to 3000 mRNAs enriched for cancer pathways. A prominent member of the LARP1 interactome is mTOR whose mRNA transcript is stabilized by LARP1. At a functional level, we show that LARP1 promotes cell migration, invasion, anchorage-independent growth and in vivo tumorigenesis. Furthermore, we show that LARP1 expression is elevated in epithelial cancers such as cervical and non-small cell lung cancers, where its expression correlates with disease progression and adverse prognosis, respectively. We therefore conclude that, through the post-transcriptional regulation of genes such as mTOR within cancer pathways, LARP1 contributes to cancer progression.

History

Citation

Oncogene, 2015, 34 (39), pp. 5025-5036

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/MBSP Non-Medical Departments/Molecular & Cell Biology

Version

VoR (Version of Record)

Published in

Oncogene

Publisher

Nature Publishing Group

issn

0950-9232

eissn

1476-5594

Acceptance date

21/10/2014

Copyright date

2015

Available date

23/02/2016

Publisher version

http://www.nature.com/onc/journal/v34/n39/full/onc2014428a.html

Language

en