The role of DDX3 in regulating Snail

Mianen Sun, Ling Song, Tong Zhou, G. Yancey Gillespie, Richard S. Jope

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

DDX3, a DEAD box protein family member, appears to promote the progression of some cancers, which may partly result from its impedance of death receptor-mediated apoptosis. We found that another mechanism by which DDX3 may aid cancer progression is by promoting increased levels of the transcription factor Snail. Snail represses expression of cellular adhesion proteins, leading to increased cell migration and metastasis of many types of cancer. Knockdown of DDX3 levels by shRNA reduced basal levels of Snail in HeLa and MCF-7 cells, and this was associated with reduced cell proliferation and migration. Snail protein and mRNA levels were increased by treatment with the HDAC inhibitors sodium butyrate or trichostatin A, and these increases were attenuated in cells with DDX3 knocked down. Treatment of cells with camptothecin was discovered to increase Snail protein levels, and this increase was diminished in cells with DDX3 knocked down. Analysis of 31 patient glioblastoma multiforme (GBM) samples revealed a significant correlation between the levels of DDX3 and Snail. Thus, DDX3 is required for basal Snail expression and increases in Snail induced by HDAC inhibitors or camptothecin, indicating that this action of DDX3 may contribute to its promotion of the progression of some cancers.

Original languageEnglish (US)
Pages (from-to)438-447
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1813
Issue number3
DOIs
StatePublished - Mar 1 2011
Externally publishedYes

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Keywords

  • Camptothecin
  • DDX3
  • HDAC
  • Metastasis
  • Snail

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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