LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression.

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.

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.

DOI

10.1038/onc.2014.428

Type

Journal article

Journal

Oncogene

Publication Date

24/09/2015

Volume

34

Pages

5025 - 5036

Keywords

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

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