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LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression

Mura, M.; Hopkins, T. G.; Michael, T.; Abd-Latip, N.; Weir, J.; Aboagye, E.; Mauri, F.; Jameson, C.; Sturge, J.; Gabra, H.; Bushell, M.; Willis, A. E.; Curry, E.; Blagden, S. P.

Authors

M. Mura

T. G. Hopkins

T. Michael

N. Abd-Latip

J. Weir

E. Aboagye

F. Mauri

C. Jameson

H. Gabra

M. Bushell

A. E. Willis

E. Curry

S. P. Blagden



Abstract

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.

Citation

Mura, M., Hopkins, T. G., Michael, T., Abd-Latip, N., Weir, J., Aboagye, E., …Blagden, S. P. (2015). LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression. Oncogene, 34(39), 5025-5036. https://doi.org/10.1038/onc.2014.428

Acceptance Date Oct 21, 2014
Online Publication Date Dec 22, 2014
Publication Date Sep 24, 2015
Deposit Date Feb 3, 2016
Publicly Available Date Mar 28, 2024
Journal Oncogene
Print ISSN 0950-9232
Electronic ISSN 1476-5594
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 34
Issue 39
Pages 5025-5036
DOI https://doi.org/10.1038/onc.2014.428
Keywords LARP1
Public URL https://hull-repository.worktribe.com/output/384689
Publisher URL http://www.nature.com/onc/journal/v34/n39/full/onc2014428a.html
Additional Information This is a copy of an open access article published in Oncogene, 2015, v.34.

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This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/





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