N-cadherin gene expression in prostate carcinoma is modulated by integrin-dependent nuclear translocation of Twist1

Nelson R. Alexander, Nhan L. Tran, Harish Rekapally, Carol E. Summers, Carlotta Glackin, Ronald L. Heimark

Research output: Contribution to journalArticle

175 Scopus citations

Abstract

The gain of N-cadherin expression in carcinomas has been shown to be important in the regulation of cell migration, invasion, and survival. Here, we show that N-cadherin mRNA expression in PC-3 prostate carcinoma cells is dependent on β1 integral-mediated cell adhesion to fibronectin and the basic helix-loop-helix transcription factor Twist1. Depletion of Twist1 mRNA by small interfering RNA resulted in decreased expression of both Twist1 and N-cadherin and the inhibition of cell migration. Whereas Twist1 gene expression was independent of β1 integrin-mediated adhesion, Twist1 protein failed to accumulate in the nuclei of cells cultured in anchorage-independent conditions. The increased nuclear accumulation of Twist1 following cell attachment was suppressed by treatment with an inhibitor of Rho kinase or a β1 integrin neutralizing antibody. The effect of Twist1 on induction of N-cadherin mRNA required an E-box cis-element located within the first intron (+2,627) of the N-cadherin gene. These data raise the possibility that integrin-mediated adhesion to interstitial matrix proteins during metastasis differentially regulates the nuclear/cytoplasmic translocation and DNA binding of Twist1, activating N-cadherin transcription.

Original languageEnglish (US)
Pages (from-to)3365-3369
Number of pages5
JournalCancer research
Volume66
Issue number7
DOIs
StatePublished - Apr 1 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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