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Article: EZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1/HDAC2 and Snail to inhibit E-cadherin

TitleEZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1/HDAC2 and Snail to inhibit E-cadherin
Authors
KeywordsE-cadherin
EZH2
HDAC
nasopharyngeal carcinoma
Snail
Issue Date2012
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2012, v. 31 n. 5, p. 583-594 How to Cite?
AbstractThe enhancer of zeste homolog 2 (EZH2) is upregulated and has an oncogenic role in several types of human cancer. However, the abnormalities of EZH2 and its underlying mechanisms in the pathogenesis of nasopharyngeal carcinoma (NPC) remain unknown. In this study, we found that high expression of EZH2 in NPC was associated closely with an aggressive and/or poor prognostic phenotype (P<0.05). In NPC cell lines, knockdown of EZH2 by short hairpin RNA was sufficient to inhibit cell invasiveness/metastasis both in vitro and in vivo, whereas ectopic overexpression of EZH2 supported NPC cell invasive capacity with a decreased expression of E-cadherin. In addition, ablation of endogenous Snail in NPC cells virtually totally prevented the repressive activity of EZH2 to E-cadherin, indicating that Snail might be a predominant mediator of EZH2 to suppress E-cadherin. Furthermore, co-immunoprecipitation (IP), chromatin IP and luciferase reporter assays demonstrated that in NPC cells, (1) EZH2 interacted with HDAC1/HDAC2 and Snail to form a repressive complex; (2) these components interact in a linear fashion, not in a triangular fashion, that is, HDAC1 or HDAC2 bridge the interaction between EZH2 and Snail; and (3) the EZH2/HDAC1/2/Snail complex could closely bind to the E-cadherin promoter by Snail, but not YY1, to repress E-cadherin. The data provided in this report suggest a critical role of EZH2 in the control of cell invasion and/or metastasis by forming a co-repressor complex with HDAC1/HDAC2/Snail to repress E-cadherin, an activity that might be responsible, at least in part, for the development and/or progression of human NPCs. © 2012 Macmillan Publishers Limited All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/150850
ISSN
2014 Impact Factor: 8.459
2014 SCImago Journal Rankings: 3.643
ISI Accession Number ID
Funding AgencyGrant Number
Foundation of Guangzhou Science and Technology Bureau, China2005Z1-E0131
973 Project of China2010CB912802
2010CB529400
Funding Information:

We thank Dr Clifford W Welsch (Michigan State University) for his valuable comments and extensive edit for the paper. This work was supported by the Foundation of Guangzhou Science and Technology Bureau, China (2005Z1-E0131 to DX and HFK) and the 973 Project of China (2010CB912802 to HFK and 2010CB529400 to XWB and MCL).

References

 

DC FieldValueLanguage
dc.contributor.authorTong, ZTen_HK
dc.contributor.authorCai, MYen_HK
dc.contributor.authorWang, XGen_HK
dc.contributor.authorKong, LLen_HK
dc.contributor.authorMai, SJen_HK
dc.contributor.authorLiu, YHen_HK
dc.contributor.authorZhang, HBen_HK
dc.contributor.authorLiao, YJen_HK
dc.contributor.authorZheng, Fen_HK
dc.contributor.authorZhu, Wen_HK
dc.contributor.authorLiu, THen_HK
dc.contributor.authorBian, XWen_HK
dc.contributor.authorGuan, XYen_HK
dc.contributor.authorLin, MCen_HK
dc.contributor.authorZeng, MSen_HK
dc.contributor.authorZeng, YXen_HK
dc.contributor.authorKung, HFen_HK
dc.contributor.authorXie, Den_HK
dc.date.accessioned2012-06-26T06:12:31Z-
dc.date.available2012-06-26T06:12:31Z-
dc.date.issued2012en_HK
dc.identifier.citationOncogene, 2012, v. 31 n. 5, p. 583-594en_HK
dc.identifier.issn0950-9232en_HK
dc.identifier.urihttp://hdl.handle.net/10722/150850-
dc.description.abstractThe enhancer of zeste homolog 2 (EZH2) is upregulated and has an oncogenic role in several types of human cancer. However, the abnormalities of EZH2 and its underlying mechanisms in the pathogenesis of nasopharyngeal carcinoma (NPC) remain unknown. In this study, we found that high expression of EZH2 in NPC was associated closely with an aggressive and/or poor prognostic phenotype (P<0.05). In NPC cell lines, knockdown of EZH2 by short hairpin RNA was sufficient to inhibit cell invasiveness/metastasis both in vitro and in vivo, whereas ectopic overexpression of EZH2 supported NPC cell invasive capacity with a decreased expression of E-cadherin. In addition, ablation of endogenous Snail in NPC cells virtually totally prevented the repressive activity of EZH2 to E-cadherin, indicating that Snail might be a predominant mediator of EZH2 to suppress E-cadherin. Furthermore, co-immunoprecipitation (IP), chromatin IP and luciferase reporter assays demonstrated that in NPC cells, (1) EZH2 interacted with HDAC1/HDAC2 and Snail to form a repressive complex; (2) these components interact in a linear fashion, not in a triangular fashion, that is, HDAC1 or HDAC2 bridge the interaction between EZH2 and Snail; and (3) the EZH2/HDAC1/2/Snail complex could closely bind to the E-cadherin promoter by Snail, but not YY1, to repress E-cadherin. The data provided in this report suggest a critical role of EZH2 in the control of cell invasion and/or metastasis by forming a co-repressor complex with HDAC1/HDAC2/Snail to repress E-cadherin, an activity that might be responsible, at least in part, for the development and/or progression of human NPCs. © 2012 Macmillan Publishers Limited All rights reserved.en_HK
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_HK
dc.relation.ispartofOncogeneen_HK
dc.subjectE-cadherinen_HK
dc.subjectEZH2en_HK
dc.subjectHDACen_HK
dc.subjectnasopharyngeal carcinomaen_HK
dc.subjectSnailen_HK
dc.subject.meshAdulten_US
dc.subject.meshAnimalsen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshCadherins - Geneticsen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshDna-Binding Proteins - Genetics - Metabolismen_US
dc.subject.meshFemaleen_US
dc.subject.meshGene Expression Regulation, Neoplasticen_US
dc.subject.meshHistone Deacetylase 1 - Genetics - Metabolismen_US
dc.subject.meshHistone Deacetylase 2 - Genetics - Metabolismen_US
dc.subject.meshHumansen_US
dc.subject.meshMaleen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred Balb Cen_US
dc.subject.meshMice, Nudeen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshMultiprotein Complexes - Metabolismen_US
dc.subject.meshNasopharyngeal Neoplasms - Genetics - Metabolism - Pathologyen_US
dc.subject.meshNeoplasm Invasivenessen_US
dc.subject.meshNeoplasm Metastasisen_US
dc.subject.meshPromoter Regions, Genetic - Geneticsen_US
dc.subject.meshProtein Bindingen_US
dc.subject.meshRna Interferenceen_US
dc.subject.meshRepressor Proteins - Metabolismen_US
dc.subject.meshTranscription Factors - Genetics - Metabolismen_US
dc.titleEZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1/HDAC2 and Snail to inhibit E-cadherinen_HK
dc.typeArticleen_HK
dc.identifier.emailGuan, XY:xyguan@hkucc.hku.hken_HK
dc.identifier.emailLin, MC:mcllin@hkucc.hku.hken_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.identifier.authorityLin, MC=rp00746en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/onc.2011.254en_HK
dc.identifier.pmid21685935-
dc.identifier.scopuseid_2-s2.0-84856533341en_HK
dc.identifier.hkuros203481-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84856533341&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume31en_HK
dc.identifier.issue5en_HK
dc.identifier.spage583en_HK
dc.identifier.epage594en_HK
dc.identifier.isiWOS:000300221800005-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridTong, ZT=36747652800en_HK
dc.identifier.scopusauthoridCai, MY=23388510500en_HK
dc.identifier.scopusauthoridWang, XG=54947616000en_HK
dc.identifier.scopusauthoridKong, LL=54796628200en_HK
dc.identifier.scopusauthoridMai, SJ=36780688900en_HK
dc.identifier.scopusauthoridLiu, YH=54948376200en_HK
dc.identifier.scopusauthoridZhang, HB=54947880100en_HK
dc.identifier.scopusauthoridLiao, YJ=36114448500en_HK
dc.identifier.scopusauthoridZheng, F=39462354900en_HK
dc.identifier.scopusauthoridZhu, W=35207905200en_HK
dc.identifier.scopusauthoridLiu, TH=36091417000en_HK
dc.identifier.scopusauthoridBian, XW=7103023096en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK
dc.identifier.scopusauthoridLin, MC=7404816359en_HK
dc.identifier.scopusauthoridZeng, MS=10642267400en_HK
dc.identifier.scopusauthoridZeng, YX=39863826600en_HK
dc.identifier.scopusauthoridKung, HF=7402514190en_HK
dc.identifier.scopusauthoridXie, D=35070710200en_HK
dc.identifier.citeulike9506101-

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