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KMID : 0624620090420100655
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BMB Reports
2009 Volume.42 No. 10 p.655 ~ p.660
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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
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Kim Sung-Ok
Choi Byung-Tae
Choi Il-Whan
Cheong Jae-Hun
Kim Gi-Young
Kwon Taeg-Kyu
Kim Nam-Deuk
Choi Yung-Hyun
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Abstract
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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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KEYWORD
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Claudin-3, Egr-1, HDAC inhibitors, Invasion, Tight junction
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