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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
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TitleEZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1/HDAC2 and Snail to inhibit E-cadherin
 
AuthorsTong, ZT2 3
Cai, MY3
Wang, XG3
Kong, LL2
Mai, SJ3
Liu, YH1
Zhang, HB1
Liao, YJ3
Zheng, F3
Zhu, W3
Liu, TH3
Bian, XW4
Guan, XY3
Lin, MC5
Zeng, MS3
Zeng, YX3
Kung, HF5 3
Xie, D3
 
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
 
CitationOncogene, 2012, v. 31 n. 5, p. 583-594 [How to Cite?]
DOI: http://dx.doi.org/10.1038/onc.2011.254
 
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.
 
ISSN0950-9232
2012 Impact Factor: 7.357
2012 SCImago Journal Rankings: 3.558
 
DOIhttp://dx.doi.org/10.1038/onc.2011.254
 
ISI Accession Number IDWOS:000300221800005
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).

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorTong, ZT
 
dc.contributor.authorCai, MY
 
dc.contributor.authorWang, XG
 
dc.contributor.authorKong, LL
 
dc.contributor.authorMai, SJ
 
dc.contributor.authorLiu, YH
 
dc.contributor.authorZhang, HB
 
dc.contributor.authorLiao, YJ
 
dc.contributor.authorZheng, F
 
dc.contributor.authorZhu, W
 
dc.contributor.authorLiu, TH
 
dc.contributor.authorBian, XW
 
dc.contributor.authorGuan, XY
 
dc.contributor.authorLin, MC
 
dc.contributor.authorZeng, MS
 
dc.contributor.authorZeng, YX
 
dc.contributor.authorKung, HF
 
dc.contributor.authorXie, D
 
dc.date.accessioned2012-06-26T06:12:31Z
 
dc.date.available2012-06-26T06:12:31Z
 
dc.date.issued2012
 
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.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationOncogene, 2012, v. 31 n. 5, p. 583-594 [How to Cite?]
DOI: http://dx.doi.org/10.1038/onc.2011.254
 
dc.identifier.citeulike9506101
 
dc.identifier.doihttp://dx.doi.org/10.1038/onc.2011.254
 
dc.identifier.epage594
 
dc.identifier.hkuros203481
 
dc.identifier.isiWOS:000300221800005
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).

 
dc.identifier.issn0950-9232
2012 Impact Factor: 7.357
2012 SCImago Journal Rankings: 3.558
 
dc.identifier.issue5
 
dc.identifier.pmid21685935
 
dc.identifier.scopuseid_2-s2.0-84856533341
 
dc.identifier.spage583
 
dc.identifier.urihttp://hdl.handle.net/10722/150850
 
dc.identifier.volume31
 
dc.languageeng
 
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofOncogene
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAdult
 
dc.subject.meshAnimals
 
dc.subject.meshBase Sequence
 
dc.subject.meshCadherins - Genetics
 
dc.subject.meshCell Line, Tumor
 
dc.subject.meshDna-Binding Proteins - Genetics - Metabolism
 
dc.subject.meshFemale
 
dc.subject.meshGene Expression Regulation, Neoplastic
 
dc.subject.meshHistone Deacetylase 1 - Genetics - Metabolism
 
dc.subject.meshHistone Deacetylase 2 - Genetics - Metabolism
 
dc.subject.meshHumans
 
dc.subject.meshMale
 
dc.subject.meshMice
 
dc.subject.meshMice, Inbred Balb C
 
dc.subject.meshMice, Nude
 
dc.subject.meshMiddle Aged
 
dc.subject.meshMolecular Sequence Data
 
dc.subject.meshMultiprotein Complexes - Metabolism
 
dc.subject.meshNasopharyngeal Neoplasms - Genetics - Metabolism - Pathology
 
dc.subject.meshNeoplasm Invasiveness
 
dc.subject.meshNeoplasm Metastasis
 
dc.subject.meshPromoter Regions, Genetic - Genetics
 
dc.subject.meshProtein Binding
 
dc.subject.meshRna Interference
 
dc.subject.meshRepressor Proteins - Metabolism
 
dc.subject.meshTranscription Factors - Genetics - Metabolism
 
dc.subjectE-cadherin
 
dc.subjectEZH2
 
dc.subjectHDAC
 
dc.subjectnasopharyngeal carcinoma
 
dc.subjectSnail
 
dc.titleEZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1/HDAC2 and Snail to inhibit E-cadherin
 
dc.typeArticle
 
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<contributor.author>Mai, SJ</contributor.author>
<contributor.author>Liu, YH</contributor.author>
<contributor.author>Zhang, HB</contributor.author>
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<contributor.author>Zheng, F</contributor.author>
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<description.abstract>The 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&lt;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. &#169; 2012 Macmillan Publishers Limited All rights reserved.</description.abstract>
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Author Affiliations
  1. Guangdong Provincial People's Hospital
  2. An Hui Medical University
  3. Sun Yat-Sen University
  4. Third Military Medical University
  5. Chinese University of Hong Kong