title: LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression.
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.
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Ovarian Cancer Action Research Centre, Imperial College London, Hammersmith Campus, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Mura
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Ovarian Cancer Action Research Centre, Imperial College London, Hammersmith Campus, London, UK.
authors.forename: T G
authors.initials: TG
authors.lastname: Hopkins
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Ovarian Cancer Action Research Centre, Imperial College London, Hammersmith Campus, London, UK.
authors.forename: T
authors.initials: T
authors.lastname: Michael
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Ovarian Cancer Action Research Centre, Imperial College London, Hammersmith Campus, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Abd-Latip
authors.affiliation: Department of Cellular Pathology, Imperial College Healthcare NHS Trust, Charing Cross Hospital, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Weir
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Cancer Research UK Laboratories, Imperial College London, Hammersmith Campus, London, UK.
authors.forename: E
authors.initials: E
authors.lastname: Aboagye
authors.affiliation: Department of Histopathology, Centre for Pathology, Imperial College London, Hammersmith Campus, London, UK.
authors.forename: F
authors.initials: F
authors.lastname: Mauri
authors.affiliation: Department of Histopathology, University College Hospital, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Jameson
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Cancer Research UK Laboratories, Imperial College London, Hammersmith Campus, London, UK.|School of Biological, Biomedical & Environmental Sciences, The Allam Building, University of Hull, Hull, UK.
authors.forename: J
authors.initials: J
authors.lastname: Sturge
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Ovarian Cancer Action Research Centre, Imperial College London, Hammersmith Campus, London, UK.
authors.forename: H
authors.initials: H
authors.lastname: Gabra
authors.affiliation: MRC Toxicology Unit, Hodgkin Building, University of Leicester, Leicester, UK.
authors.forename: M
authors.initials: M
authors.lastname: Bushell
authors.affiliation: MRC Toxicology Unit, Hodgkin Building, University of Leicester, Leicester, UK.
authors.forename: A E
authors.initials: AE
authors.lastname: Willis
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Ovarian Cancer Action Research Centre, Imperial College London, Hammersmith Campus, London, UK.
authors.forename: E
authors.initials: E
authors.lastname: Curry
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, Ovarian Cancer Action Research Centre, Imperial College London, Hammersmith Campus, London, UK.
authors.forename: S P
authors.initials: SP
authors.lastname: Blagden
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000502:physiology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics; D012261:Ribonucleoproteins / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*; D000097585:SS-B Antigen
chemical_list: D001324:Autoantigens; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D058570:TOR Serine-Threonine Kinases; D000097585:SS-B Antigen; C546842:MTOR protein, human