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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Anti-invasive activity of histone deacetylase inhibitors via the induction of Egr-1 and the modulation of tight junction-related proteins in human hepatocarcinoma cells

  • Kim, Sung-Ok (Department of Biomaterial Control (BK21 Program), Dongeui University Graduate School) ;
  • Choi, Byung-Tae (Department of Anatomy, Graduate School of Oriental Medicine, Pusan National University) ;
  • Choi, Il-Whan (Department of Microbiology, College of Medicine and Center for Viral Disease Research, Inje University) ;
  • Cheong, Jae-Hun (Department of Molecular Biology, Pusan National University) ;
  • Kim, Gi-Young (Faculty of Applied Marine Science, Cheju National University) ;
  • Kwon, Taeg-Kyu (Department of Immunology, School of Medicine, Keimyung University) ;
  • Kim, Nam-Deuk (Division of Pharmacy, Pusan National University) ;
  • Choi, Yung-Hyun (Department of Biomaterial Control (BK21 Program), Dongeui University Graduate School)
  • Published : 2009.10.31
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Abstract

The potential anti-metastasis and anti-invasion activities of early growth response gene-1 (Egr-1) and claudin-3, a tight junction (TJ)-related protein, were evaluated using histone deacetylase (HDAC) inhibitors in human hepatocarcinoma cells. The results of wound healing and Transwell assays showed that HDAC inhibitors such as trichostatin A and sodium butyrate inhibited cell migration and invasion. HDAC inhibitors markedly induced Egr-1 expression during the early period, after which expression levels decreased. In addition, the down-regulation of snail and type 1 insulin-like growth factor receptor (IGF-1R) in HDAC inhibitor- treated cells induced the upregulation of thrombospondin-1 (TSP-1), E-cadherin and claudin-3. Cells transfected with Egr-1 and claudin-3 siRNA displayed significant blockage of HDAC inhibitor-induced anti-invasive activity. Collectively, these findings indicate that the up-regulation of Egr-1 and claudin-3 are crucial steps in HDAC inhibitor-induced anti-metastasis and anti-invasion.

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References

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