Regulation of local expression of cell adhesion and motility-related mRNAs in breast cancer cells by IMP1/ZBP1

Wei Gu, Zachary Katz, Bin Wu, Hye Yoon Park, Deling Li, Stanley Lin, Amber L. Wells, Robert H. Singer

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Metastasis involves tumor cell detachment from the primary tumor, and acquisition of migratory and invasive capabilities. These capabilities are mediated by multiple events, including loss of cell-cell contact, an increase in focal adhesion turnover and failure to maintain a normal cell polarity. We have previously reported that silencing of the expression of the zipcode-binding protein IMP1/ZBP1 in breast tumor patients is associated with metastasis. IMP1/ZBP1 selectively binds to a group of mRNAs that encode important mediators for cell adhesion and motility. Here, we show that in both T47D and MDA231 human breast carcinoma cells IMP1/ZBP1 functions to suppress cell invasion. Binding of ZBP1 to the mRNAs encoding E-cadherin, β-actin, α-actinin and the Arp2/3 complex facilitates localization of the mRNAs, which stabilizes cell-cell connections and focal adhesions. Our studies suggest a novel mechanism through which IMP1/ZBP1 simultaneously regulates the local expression of many cell-motility-related mRNAs to maintain cell adherence and polarity, decrease focal adhesion turnover and maintain a persistent and directional motility.

Original languageEnglish (US)
Pages (from-to)81-91
Number of pages11
JournalJournal of cell science
Volume125
Issue number1
DOIs
StatePublished - Jan 1 2012

Keywords

  • Cancer cell invasion
  • Mrna localization
  • Post-transcriptional regulation

ASJC Scopus subject areas

  • Cell Biology

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