Blocking β-catenin binding to the ZBP1 promoter represses ZBP1 expression, leading to increased proliferation and migration of metastatic breast-cancer cells

Wei Gu, Feng Pan, Robert H. Singer

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

ZBP1 (zipcode-binding protein 1, also known as IMP-1) is an mRNA regulator, functioning in mRNA localization, stability and translational control. ZBP1 is actively expressed during embryogenesis and tumorigenesis, but its expression is repressed in metastatic breast-cancer cell lines and tumors. In this article, we show that downregulation of ZBP1 expression results from its promoter methylation, an epigenetic process that remodels the chromatin structure and frequently represses gene activity. Demethylation of the ZBP1 promoter in metastatic cells reactivated ZBP1 expression, owing to restoration of the interaction of the ZBP1 promoter with β-catenin. Loss of ZBP1 function not only increased growth ability of metastatic cells, but also promoted cell migration. We identified a number of mRNAs that were selectively associated with ZBP1 in breast-cancer cells. Many of these are involved in cell motility and in cell-cycle regulation, and displayed altered expression patterns in the absence of ZBP1. These data suggest that repression of ZBP1 deregulates its associated mRNAs, leading to the phenotypic changes of breast cancers.

Original languageEnglish (US)
Pages (from-to)1895-1905
Number of pages11
JournalJournal of cell science
Volume122
Issue number11
DOIs
StatePublished - Jun 1 2009

Keywords

  • Cell proliferation
  • Metastasis
  • Promoter methylation
  • Wnt-β-catenin signaling
  • ZBP1 repression

ASJC Scopus subject areas

  • Cell Biology

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