LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression

Oncogene. 2015 Sep 24;34(39):5025-36. doi: 10.1038/onc.2014.428. Epub 2014 Dec 22.

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 types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens / physiology*
  • Disease Progression
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasms / pathology*
  • RNA Processing, Post-Transcriptional*
  • RNA, Messenger / genetics
  • Ribonucleoproteins / physiology*
  • SS-B Antigen
  • TOR Serine-Threonine Kinases / physiology*

Substances

  • Autoantigens
  • RNA, Messenger
  • Ribonucleoproteins
  • MTOR protein, human
  • TOR Serine-Threonine Kinases