Polycomb group protein EZH2-mediated E-cadherin repression promotes metastasis of oral tongue squamous cell carcinoma.
Polycomb group protein EZH2-mediated E-cadherin repression promotes metastasis of oral tongue squamous cell carcinoma.
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DOI：
10.1002/mc.21848
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发表时间：
2013-03
影响因子：
4.6
通讯作者：
Zhou, Xiaofeng
中科院分区：
文献类型：
--
作者：
Wang, Cheng;Liu, Xiqiang;Chen, Zujian;Huang, Hongzhang;Jin, Yi;Kolokythas, Antonia;Wang, Anxun;Dai, Yang;Wong, David T. W.;Zhou, Xiaofeng
Zeste增强子同源物2（EZH 2）是多梳抑制复合物2（PRC 2）的关键组分，其调节许多基本生物学过程，包括胚胎发生和许多发育事件。EZH 2的致癌作用最近已涉及几种癌症类型。在本研究中，我们首次证实了EZH 2的过度表达是口腔舌鳞状细胞癌（OTSCC）的常见事件。我们进一步证明EZH 2过表达与疾病的晚期相关，并与淋巴结转移相关。统计分析显示EZH 2过表达与总生存率降低相关。此外，EZH 2的过度表达与肿瘤抑制基因E-cadherin的表达降低相关。这些观察结果在体外得到证实，其中EZH 2的敲低诱导E-钙粘蛋白表达并减少细胞迁移和侵袭。相反，EZH 2的异位转染导致E-钙粘蛋白表达减少，并增强细胞迁移和侵袭。此外，EZH 2可能通过抑制E-钙粘蛋白表达而部分地作用于细胞迁移。总之，这些数据表明EZH 2在OTSCC的进展中起主要作用，并且可以作为具有转移风险的患者的生物标志物或治疗靶标。
Enhancer of zeste homolog 2 (EZH2) is a critical component of the polycomb-repressive complex 2 (PRC2) that regulates many essential biological processes, including embryogenesis and many developmental events. The oncogenic role of EZH2 has recently been implicated in several cancer types. In this study, we first confirmed that the over-expression of EZH2 is a frequent event in oral tongue squamous cell carcinoma (OTSCC). We further demonstrated that EZH2 over-expression is correlated with advanced stages of the disease and is associated with lymph node metastasis. Statistical analysis revealed that EZH2 over-expression was correlated with reduced overall survival. Furthermore, over-expression of EZH2 was correlated with reduced expression of tumor suppressor gene E-cadherin. These observations were confirmed in vitro, in which knockdown of EZH2 induced E-cadherin expression and reduced cell migration and invasion. In contrast, ectopic transfection of EZH2 led to reduced E-cadherin expression and enhanced cell migration and invasion. Furthermore, EZH2 may act on cell migration in part by suppressing the E-cadherin expression. Taken together, these data suggest that EZH2 plays major roles in the progression of OTSCC, and may serve as a biomarker or therapeutic target for patients at risk of metastasis.
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影响因子：
3
作者：
Yuen, APW;Lam, KY;Ho, CM
通讯作者：
Ho, CM
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2.6
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Lenox, J
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64.8
作者：
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通讯作者：
Chinnaiyan, AM
影响因子：
9.7
作者：
Liu, Xiqiang;Jiang, Lu;Wang, Anxun;Yu, Jinsheng;Shi, Fei;Zhou, Xiaofeng
通讯作者：
Zhou, Xiaofeng