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.

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., Mauri, F., Jameson, C., Sturge, J., Gabra, H., Bushell, M., Willis, A. E., Curry, 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: Nov 23, 2017
• Journal: Oncogene
• Print ISSN: 0950-9232
• 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.
• Contract Date: Nov 23, 2017