Histone deacetylase 6 functions as a tumor suppressor by activating c-Jun NH2-terminal kinase-mediated beclin 1-dependent autophagic cell death in liver cancer

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dc.contributor.authorK H Jung-
dc.contributor.authorJ H Noh-
dc.contributor.authorJ K Kim-
dc.contributor.authorJ W Eun-
dc.contributor.authorH J Bae-
dc.contributor.authorY G Chang-
dc.contributor.authorM G Kim-
dc.contributor.authorW S Park-
dc.contributor.authorJ Y Lee-
dc.contributor.authorSang Yoep Lee-
dc.contributor.authorIn-Sun Chu-
dc.contributor.authorS W Nam-
dc.date.accessioned2017-04-19T09:33:01Z-
dc.date.available2017-04-19T09:33:01Z-
dc.date.issued2012-
dc.identifier.issn0270-9139-
dc.identifier.uri10.1002/hep.25699ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/10872-
dc.description.abstractUbiquitin-binding histone deacetylase 6 (HDAC6) is uniquely endowed with tubulin deacetylase activity and plays an important role in the clearance of misfolded protein by autophagy. In cancer, HDAC6 has become a target for drug development due to its major contribution to oncogenic cell transformation. In the present study we show that HDAC6 expression was down-regulated in a large cohort of human hepatocellular carcinoma (HCC) patients, and that low expression of HDAC6 was significantly associated with poor prognosis of HCC patients in 5-year overall, disease-free, and recurrence-free survival. Notably, we observed that ectopic overexpression of HDAC6 suppressed tumor cell growth and proliferation in various liver cancer cells, and elicited increased LC3B-II conversion and autophagic vacuole formation without causing apoptotic cell death or cell cycle inhibition. In addition, the sustained overexpression of HDAC6 reduced the in vivo tumor growth rate in a mouse xenograft model. It was also found that HDAC6 mediated autophagic cell death by way of Beclin 1 and activation of the LC3-II pathway in liver cancer cells, and that HDAC6 overexpression activated c-Jun NH2-terminal kinase (JNK) and increased the phosphorylation of c-Jun. In contrast, the induction of Beclin 1 expression was blocked by SP600125 (a specific inhibitor of JNK) or by small interfering RNA directed against HDAC6. Conclusion: Our findings suggest that loss of HDAC6 expression in human HCCs and tumor suppression by HDAC6 occur by way of activation of caspase-independent autophagic cell death through the JNK/Beclin 1 pathway in liver cancer and, thus, that a novel tumor suppressor function mechanism involving HDAC6 may be amenable to nonepigenetic regulation.-
dc.publisherWiley-
dc.titleHistone deacetylase 6 functions as a tumor suppressor by activating c-Jun NH2-terminal kinase-mediated beclin 1-dependent autophagic cell death in liver cancer-
dc.title.alternativeHistone deacetylase 6 functions as a tumor suppressor by activating c-Jun NH2-terminal kinase-mediated beclin 1-dependent autophagic cell death in liver cancer-
dc.typeArticle-
dc.citation.titleHepatology-
dc.citation.number2-
dc.citation.endPage657-
dc.citation.startPage644-
dc.citation.volume56-
dc.contributor.affiliatedAuthorSang Yoep Lee-
dc.contributor.affiliatedAuthorIn-Sun Chu-
dc.contributor.alternativeName정광화-
dc.contributor.alternativeName노지헌-
dc.contributor.alternativeName김정규-
dc.contributor.alternativeName은정우-
dc.contributor.alternativeName배현진-
dc.contributor.alternativeName장영균-
dc.contributor.alternativeName김민규-
dc.contributor.alternativeName박원상-
dc.contributor.alternativeName이정영-
dc.contributor.alternativeName이상엽-
dc.contributor.alternativeName추인선-
dc.contributor.alternativeName남석우-
dc.identifier.bibliographicCitationHepatology, vol. 56, no. 2, pp. 644-657-
dc.identifier.doi10.1002/hep.25699-
dc.description.journalClassY-
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Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
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