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

Oncogene volume 31, pages 583–594 (2012)Cite this article

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.

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Acknowledgements

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).

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Author notes

  1. Z-T Tong and M-Y Cai: These authors contributed equally to this work.

Authors and Affiliations

  1. The State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, China

    Z-T Tong, M-Y Cai, S-J Mai, Y-J Liao, F Zheng, W Zhu, T-H Liu, X-Y Guan, M-S Zeng, Y-X Zeng, H-F Kung & D Xie

  2. Department of Experimental Research, Cancer Center, Sun Yat-Sen University, Guangzhou, China

    Z-T Tong, S-J Mai, Y-J Liao, F Zheng, W Zhu, T-H Liu, X-Y Guan, M-S Zeng, Y-X Zeng & D Xie

  3. Department of Radiotherapy, the First Affiliated Hospital, An Hui Medical University, Hefei, China

    Z-T Tong & L-L Kong

  4. Department of Pharmacology, Zhong Shan School of Medicine, Sun Yat-Sen University, Guangzhou, China

    X-G Wang

  5. Department of Pathology, Guangdong Provincial People's Hospital, Guangzhou, China

    Y-H Liu

  6. Department of Otolaryngology, Guangdong Provincial People's Hospital, Guangzhou, China

    H-B Zhang

  7. Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China

    X-W Bian

  8. The State Key Laboratory of Oncology in South China, the Chinese University of Hong Kong, Hong Kong, China

    M C Lin & H-F Kung

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Correspondence to D Xie.

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Tong, ZT., Cai, MY., Wang, XG. et al. EZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1/HDAC2 and Snail to inhibit E-cadherin. Oncogene 31, 583–594 (2012). https://doi.org/10.1038/onc.2011.254

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