Article: EZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1/HDAC2 and Snail to inhibit E-cadherin
| Title | EZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1/HDAC2 and Snail to inhibit E-cadherin | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Tong, 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, HF3 5 Xie, D3 | ||||||
| Keywords | E-cadherin EZH2 HDAC nasopharyngeal carcinoma Snail | ||||||
| Issue Date | 2012 | ||||||
| Publisher | Nature 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?] DOI: http://dx.doi.org/10.1038/onc.2011.254 | ||||||
| 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<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. | ||||||
| ISSN | 0950-9232 2011 Impact Factor: 6.373 2011 SCImago Journal Rankings: 1.216 | ||||||
| DOI | http://dx.doi.org/10.1038/onc.2011.254 | ||||||
| ISI Accession Number ID | WOS:000300221800005
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 | References in Scopus |
| dc.contributor.author | Tong, ZT | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Cai, MY | ||||||
| dc.contributor.author | Wang, XG | ||||||
| dc.contributor.author | Kong, LL | ||||||
| dc.contributor.author | Mai, SJ | ||||||
| dc.contributor.author | Liu, YH | ||||||
| dc.contributor.author | Zhang, HB | ||||||
| dc.contributor.author | Liao, YJ | ||||||
| dc.contributor.author | Zheng, F | ||||||
| dc.contributor.author | Zhu, W | ||||||
| dc.contributor.author | Liu, TH | ||||||
| dc.contributor.author | Bian, XW | ||||||
| dc.contributor.author | Guan, XY | ||||||
| dc.contributor.author | Lin, MC | ||||||
| dc.contributor.author | Zeng, MS | ||||||
| dc.contributor.author | Zeng, YX | ||||||
| dc.contributor.author | Kung, HF | ||||||
| dc.contributor.author | Xie, D | ||||||
| dc.date.accessioned | 2012-06-26T06:12:31Z | ||||||
| dc.date.available | 2012-06-26T06:12:31Z | ||||||
| dc.date.issued | 2012 | ||||||
| dc.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<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.nature | Link_to_subscribed_fulltext | ||||||
| dc.identifier.citation | Oncogene, 2012, v. 31 n. 5, p. 583-594 [How to Cite?] DOI: http://dx.doi.org/10.1038/onc.2011.254 | ||||||
| dc.identifier.citeulike | 9506101 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1038/onc.2011.254 | ||||||
| dc.identifier.epage | 594 | ||||||
| dc.identifier.hkuros | 203481 | ||||||
| dc.identifier.isi | WOS:000300221800005
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.issn | 0950-9232 2011 Impact Factor: 6.373 2011 SCImago Journal Rankings: 1.216 | ||||||
| dc.identifier.issue | 5 | ||||||
| dc.identifier.pmid | 21685935 | ||||||
| dc.identifier.scopus | eid_2-s2.0-84856533341 | ||||||
| dc.identifier.spage | 583 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/150850 | ||||||
| dc.identifier.volume | 31 | ||||||
| dc.language | eng | ||||||
| dc.publisher | Nature Publishing Group. The Journal's web site is located at http://www.nature.com/onc | ||||||
| dc.publisher.place | United Kingdom | ||||||
| dc.relation.ispartof | Oncogene | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.subject.mesh | Adult | ||||||
| dc.subject.mesh | Animals | ||||||
| dc.subject.mesh | Base Sequence | ||||||
| dc.subject.mesh | Cadherins - Genetics | ||||||
| dc.subject.mesh | Cell Line, Tumor | ||||||
| dc.subject.mesh | Dna-Binding Proteins - Genetics - Metabolism | ||||||
| dc.subject.mesh | Female | ||||||
| dc.subject.mesh | Gene Expression Regulation, Neoplastic | ||||||
| dc.subject.mesh | Histone Deacetylase 1 - Genetics - Metabolism | ||||||
| dc.subject.mesh | Histone Deacetylase 2 - Genetics - Metabolism | ||||||
| dc.subject.mesh | Humans | ||||||
| dc.subject.mesh | Male | ||||||
| dc.subject.mesh | Mice | ||||||
| dc.subject.mesh | Mice, Inbred Balb C | ||||||
| dc.subject.mesh | Mice, Nude | ||||||
| dc.subject.mesh | Middle Aged | ||||||
| dc.subject.mesh | Molecular Sequence Data | ||||||
| dc.subject.mesh | Multiprotein Complexes - Metabolism | ||||||
| dc.subject.mesh | Nasopharyngeal Neoplasms - Genetics - Metabolism - Pathology | ||||||
| dc.subject.mesh | Neoplasm Invasiveness | ||||||
| dc.subject.mesh | Neoplasm Metastasis | ||||||
| dc.subject.mesh | Promoter Regions, Genetic - Genetics | ||||||
| dc.subject.mesh | Protein Binding | ||||||
| dc.subject.mesh | Rna Interference | ||||||
| dc.subject.mesh | Repressor Proteins - Metabolism | ||||||
| dc.subject.mesh | Transcription Factors - Genetics - Metabolism | ||||||
| dc.subject | E-cadherin | ||||||
| dc.subject | EZH2 | ||||||
| dc.subject | HDAC | ||||||
| dc.subject | nasopharyngeal carcinoma | ||||||
| dc.subject | Snail | ||||||
| dc.title | EZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1/HDAC2 and Snail to inhibit E-cadherin | ||||||
| dc.type | Article |
Author Affiliations
- Guangdong Provincial People's Hospital
- An Hui Medical University
- Sun Yat-Sen University
- Third Military Medical University
- Chinese University of Hong Kong