LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression

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Title: LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression
Author(s): Mura, M
Hopkins, TG
Michael, T
Abd-Latip, N
Weir, J
Aboagye, E
Mauri, F
Jameson, C
Sturge, J
Gabra, H
Bushell, M
Willis, AE
Curry, E
Blagden, SP
Item Type: Journal Article
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.
Publication Date: 22-Dec-2014
Date of Acceptance: 21-Oct-2014
URI: http://hdl.handle.net/10044/1/43636
DOI: https://dx.doi.org/10.1038/onc.2014.428
ISSN: 1476-5594
Publisher: Nature Publishing Group
Start Page: 5025
End Page: 5036
Journal / Book Title: Oncogene
Volume: 34
Copyright Statement: © 2015 Macmillan Publishers Limited. 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/.
Sponsor/Funder: GlaxoSmithKline Services Unlimited
Wellbeing of Women
Funder's Grant Number: COL011953
RG1319
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Oncology
Cell Biology
Genetics & Heredity
MESSENGER-RNA STABILITY
GENE-EXPRESSION
CERVICAL-CANCER
EARLY-STAGE
BINDING PROTEINS
MAMMALIAN-CELLS
TRANSLATION
TARGET
DECAY
SPECIMENS
Animals
Autoantigens
Disease Progression
Female
Humans
Mice
Mice, Inbred BALB C
Neoplasm Invasiveness
Neoplasm Metastasis
Neoplasms
RNA Processing, Post-Transcriptional
RNA, Messenger
Ribonucleoproteins
TOR Serine-Threonine Kinases
Animals
Mice, Inbred BALB C
Humans
Mice
Neoplasms
Neoplasm Invasiveness
Neoplasm Metastasis
Disease Progression
Ribonucleoproteins
RNA, Messenger
Autoantigens
RNA Processing, Post-Transcriptional
Female
TOR Serine-Threonine Kinases
Oncology & Carcinogenesis
1112 Oncology And Carcinogenesis
1103 Clinical Sciences
Publication Status: Published
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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