LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression

• DOI: 10.1038/onc.2014.428
• Publication Date: 2014-12-22T13:58:43Z
• Authors: M Mura; T G Hopkins; T Michael; N Abd-Latip; J Weir; E Aboagye; F Mauri; C Jameson; J Sturge; H Gabra; M Bushell; A E Willis; E Curry; S P Blagden
• Keywords: 0301 basic medicine; 570; RNA Processing; Biochemistry & Molecular Biology; CERVICAL-CANCER; Messenger; Post-Transcriptional; 610; Autoantigens; LARP1; SS-B Antigen; MESSENGER-RNA STABILITY; Mice; 03 medical and health sciences; MAMMALIAN-CELLS; Neoplasms; Animals; Humans; Neoplasm Invasiveness; Oncology & Carcinogenesis; RNA, Messenger; Neoplasm Metastasis; RNA Processing, Post-Transcriptional; Inbred BALB C; GENE-EXPRESSION; Genetics & Heredity; Mice, Inbred BALB C; Science & Technology; TOR Serine-Threonine Kinases; BINDING PROTEINS; 1103 Clinical Sciences; Cell Biology; SPECIMENS; 3. Good health; TARGET; Oncology; Ribonucleoproteins; Disease Progression; RNA; EARLY-STAGE; Original Article; Female; TRANSLATION; Life Sciences & Biomedicine; DECAY; 1112 Oncology And Carcinogenesis

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.