May 23, 2009

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

Journal of Cell Science
Wei GuRobert H Singer

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 beta-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.

  • References48
  • Citations21

References

Mentioned in this Paper

Establishment and Maintenance of Localization
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Beta catenin
Protein Methylation
Cell Motility
Cosuppression
Neoplasms
DNA Methylation
Promoter

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