PCBP1 suppresses the translation of metastasis-associated PRL-3 phosphatase

Cancer Cell. 2010 Jul 13;18(1):52-62. doi: 10.1016/j.ccr.2010.04.028.

Abstract

Overexpression of phosphatase of regenerating liver (PRL)-3 is associated with the progression of diverse human cancers. We show that the overexpression of PRL-3 protein is not directly associated with its transcript levels, indicating the existence of an underlying posttranscriptional regulation. The 5' untranslanted region (UTR) of PRL-3 mRNA possesses triple GCCCAG motifs capable of suppressing mRNA translation through interaction with PolyC-RNA-binding protein 1 (PCBP1), which retards PRL-3 mRNA transcript incorporation into polyribosomes. Overexpression of PCBP1 inhibits PRL-3 expression and inactivates AKT, whereas knockdown of PCBP1 causes upregulation of PRL-3 protein levels, activation of AKT, and promotion of tumorigenesis. An inverse correlation between protein levels of PRL-3 and PCBP1 in human primary cancers supports the clinical relevance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / genetics
  • Animals
  • Blotting, Western
  • Cell Line, Tumor
  • DNA-Binding Proteins
  • Electrophoretic Mobility Shift Assay
  • Gene Expression Regulation, Neoplastic
  • Heterogeneous-Nuclear Ribonucleoproteins / genetics
  • Heterogeneous-Nuclear Ribonucleoproteins / metabolism*
  • Humans
  • Immunoenzyme Techniques
  • Luciferases / metabolism
  • Lymphatic Metastasis
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Polyribosomes / metabolism
  • Promoter Regions, Genetic
  • Protein Biosynthesis*
  • Protein Tyrosine Phosphatases / antagonists & inhibitors
  • Protein Tyrosine Phosphatases / genetics*
  • Protein Tyrosine Phosphatases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / genetics
  • RNA, Small Interfering / pharmacology
  • RNA-Binding Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Tissue Array Analysis
  • Xenograft Model Antitumor Assays

Substances

  • 5' Untranslated Regions
  • DNA-Binding Proteins
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Neoplasm Proteins
  • PCBP1 protein, human
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Luciferases
  • Proto-Oncogene Proteins c-akt
  • PTP4A3 protein, human
  • Protein Tyrosine Phosphatases