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

164 Citations (Scopus)

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

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Cadherins
Integrins
Prostate
Carcinoma
Gene Expression
Messenger RNA
E-Box Elements
Cell Migration Inhibition
Basic Helix-Loop-Helix Transcription Factors
rho-Associated Kinases
Neutralizing Antibodies
Cell Nucleus
Fibronectins
Cell Adhesion
Introns
Small Interfering RNA
Cell Movement
Cultured Cells
Cell Survival
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

N-cadherin gene expression in prostate carcinoma is modulated by integrin-dependent nuclear translocation of Twist1. / Alexander, Nelson R.; Tran, Nhan L.; Rekapally, Harish; Summers, Carol E.; Glackin, Carlotta; Heimark, Ronald L.

In: Cancer Research, Vol. 66, No. 7, 01.04.2006, p. 3365-3369.

Research output: Contribution to journalArticle

Alexander, Nelson R. ; Tran, Nhan L. ; Rekapally, Harish ; Summers, Carol E. ; Glackin, Carlotta ; Heimark, Ronald L. / N-cadherin gene expression in prostate carcinoma is modulated by integrin-dependent nuclear translocation of Twist1. In: Cancer Research. 2006 ; Vol. 66, No. 7. pp. 3365-3369.
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