Hepatitis C virus core protein downregulates E-cadherin expression via activation of DNA methyltransferase 1 and 3b
Abstract E-cadherin is a major cell adhesion molecule implicated as a potent tumor suppressor, which is frequently altered in human tumors including hepatocellular carcinoma. Here, we report that hepatitis C virus Core downregulates E-cadherin expression at the transcription level. This effect was a...
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Veröffentlicht in: | Cancer letters 2008-03, Vol.261 (2), p.244-252 |
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Sprache: | eng |
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Zusammenfassung: | Abstract E-cadherin is a major cell adhesion molecule implicated as a potent tumor suppressor, which is frequently altered in human tumors including hepatocellular carcinoma. Here, we report that hepatitis C virus Core downregulates E-cadherin expression at the transcription level. This effect was abolished after treatment of 5′-Aza-2′dC, a specific inhibitor of DNA methyltransferase (DNMT). In addition, this repression was strongly correlated with hypermethylation of CpG islands of E-cadherin promoter via concerted action of both DNMT1 and 3b in Core-expressing cells. The decreased E-cadherin expression results in dramatic morphological changes in Core-expressing cells. In addition, Core-expressing cells aggregate poorly in suspension culture, reflecting their altered cell–cell interactions. The biological significance was further demonstrated by the increased collagen invasion ability of Core-expressing cells. Therefore, our finding suggests that Core plays a role in hepatocellular carcinogenesis by favoring cell detachment from the surrounding cells and migration outside of the primary tumor site. |
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ISSN: | 0304-3835 1872-7980 |
DOI: | 10.1016/j.canlet.2007.11.033 |