Enhancer of Zeste Homolog 2 Overexpression in Nasopharyngeal Carcinoma: An Independent Poor Prognosticator That Enhances Cell Growth

Hwang, Chung‐Feng; Huang, Hsuan-Ying; Chen, Chang‐Han; Chien, Chih‐Yen; Hsu, Yao-Chung; Li, Chien‐Feng; Fang, Fu‐Min

doi:10.1016/j.ijrobp.2010.11.062

Cited by 26 publications

(22 citation statements)

References 27 publications

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“…This is independent of the proposed effects of EZH2 on actin polymerization, which may also play a role in cancer cell motility and invasion. 28 An alternate pathway implicated in EC pathogenesis is the Wnt pathway. Dysregulation of the Wnt pathway has been associated with a variety of human malignancies.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Enhancer of Zeste Homolog 2 (EZH2) Expression Is Associated With Decreased Tumor Cell Proliferation, Migration, and Invasion in Endometrial Cancer Cell Lines

Eskander

Huynh

et al. 2013

International Journal of Gynecological Cancer

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Objective To investigate the impact of Enhancer of Zeste Homolog 2 (EZH2) expression on endometrial cancer cell line behavior. Methods/materials EZH2 expression levels were compared between the non-malignant endometrial cell line T-HESC, and 3 endometrial cancer cell lines, ECC-1, RL95-2 and HEC1-A. Stable EZH2 knockdown cell lines were created and the impact on cellular proliferation, migration and invasion were determined. Fluorescent activated cell sorting was used to examine effects of EZH2 silencing on cell cycle progression. EZH2 expression in endometrial cancer tissue specimens was examined using immunohistochemistry. Comparison of differences between control and shEZH2 cell lines was performed using student's t test and Fischer's exact test. Results EZH2 protein expression was increased in all 3 cancer cell lines, and human endometrial cancer tissue specimens relative to control. RNA interference of EZH2 expression in ECC-1, RL95-2, and HEC1-A significantly decreased cell proliferation, migration and invasion. Down regulation of EZH2 expression resulted in a significant increase in the proportion of cells arrested in G2/M. RNA interference of EZH2 expression was associated with an increase in the expression of Wnt pathway inhibitors sFRP1 and DKK3, and a concomitant decrease in β-catenin. EZH2 expression in human tissue samples was significantly associated with increased stage, grade, depth of invasion and nodal metastasis. Conclusions EZH2 expression is associated with tumor cell proliferation, migration and invasion in 3 endometrial cancer cell lines, as well as increased stage, grade, depth of invasion and nodal metastasis in human cancer tissue specimens. Further investigation into this potential therapeutic target is warranted.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Enhancer of Zeste Homolog 2 (EZH2) Expression Is Associated With Decreased Tumor Cell Proliferation, Migration, and Invasion in Endometrial Cancer Cell Lines

Eskander

Huynh

et al. 2013

International Journal of Gynecological Cancer

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“…Reports showed that EZH2 inhibitors, such as suberoylanilide hydroxamic acid (SAHA) and 3-deazaneplanocin A (DZNep), exerted anticancer effects through activation of tumor-suppressor microRNAs (miRNAs) in gastric and liver cancer cells 27 . EZH2 contributes to tumor development and progression, and represents an independent prognostic marker in patients with NPC 24 . Thus, targeting EZH2 may be considered as an additional therapeutic potential for the treatment and prevention of NPC.…”

Section: Introductionmentioning

confidence: 99%

Interplay of DNA methyltransferase 1 and EZH2 through inactivation of Stat3 contributes to β-elemene-inhibited growth of nasopharyngeal carcinoma cells

Tang

Yang

et al. 2017

Sci Rep

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β-elemene, a compound extracted from Curcuma wenyujin plant, exhibits anticancer activity in many cancer types. However, the detailed mechanism by which β-elemene inhibits growth of nasopharyngeal carcinoma (NPC) cells remains unknown. We showed that β-elemene reduced phosphorylation of signal transducer and activator of transcription 3 (Stat3), and protein expressions of DNA methyltransferase 1 (DNMT1) and enhancer of zeste homolog 2 (EZH2). Exogenously expressed Stat3 antagonized the effect of β-elemene on DNMT1 and EZH2 expressions. Furthermore, overexpressions of DNMT1 and EZH2 reversed the effect of β-elemene on phosphorylation of Stat3 and cell growth inhibition. Intriguingly, exogenously expressed DNMT1 overcame β-elemene-inhibited EZH2 protein expression and promoter activity. On the contrary, silencing of EZH2 and DNMT1 genes feedback strengthened the effect of β-elemene on phosphorylation of Stat3. Consistent with this, β-elemene inhibited tumor growth, phosphorylation of Stat3, expressions of DNMT1 and EZH2 in a mouse xenograft model. Collectively, this study shows that β-elemene inhibits NPC cell growth via inactivation of Stat3, and reduces DNMT1 and EZH2 expressions. The interplay of DNMT1 and EZH2, and the mutual regulations among Stat3, EZH2 and DNMT1 contribute to the overall responses of β-elemene. This study uncovers a novel mechanism by which β-elemene inhibits growth of NPC cells.

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“…Overexpression of EZH2 was associated with an advanced clinical stage and increased risk of relapse, and EZH2 served as an independent poor prognostic factor for patients with NPC (3,22). Therefore, ROCK1 may be partially involved in EZH2-induced progression of NPC.…”

Section: Discussionmentioning

confidence: 98%

“…Previous studies have identified that EZH2 was overexpressed in a variety of carcinomas including NPC, prostate cancer and breast cancer. The expression levels of EZH2 were associated with tumor size, depth of invasion, tumor stage, lymph node metastasis, migration and invasion ability, suggesting that EZH2 had the potential to be a novel diagnosis biomarker and a target for antitumor therapy in NPC (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of extracts of Celastrusï¿½orbiculatus in suppressing migration and invasion by inhibiting the EZH2/ROCK1 signaling pathway in human nasopharyngeal carcinoma

et al. 2018

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Abstract. Celastrus orbiculatus extract (COE) has been used in folk medicine in China for the treatment of a number of diseases. In the laboratory, COE exhibits a variety of anticancer functions, including inhibition of metastasis. However, the underlying molecular anti-metastatic mechanism in nasopharyngeal carcinoma (NPC) cells remains unclear. The aim of the present study was to determine whether the anti-metastatic effect of COE was involved in inhibiting migration and invasion of human NPC cells. In vitro, cell viability and apoptosis of 5-8F cells were analyzed using an MTS assay and flow cytometry, respectively. Invasion and migration of 5-8F cells were analyzed using a Transwell assay. Protein and mRNA expression levels of 5-8F cells were analyzed by western blot analysis and the reverse transcription-quantitative polymerase chain reaction, respectively. COE significantly decreased cell viability in 5-8F cells and inhibited enhancer of zeste homolog 2 (EZH2) and Rho-associated coiled coil-containing protein kinase 1 (ROCK1) expression at the mRNA and protein levels. Furthermore, COE decreased the migration and invasion of 5-8F cells in a dose-dependent manner. The results of the present study suggested that COE prevents migration and invasion by suppressing the EZH2/ROCK1 signaling pathway in NPC cells. On the basis of the results of the present study, COE may be a novel anticancer agent for the treatment of metastasis in NPC.

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Enhancer of Zeste Homolog 2 Overexpression in Nasopharyngeal Carcinoma: An Independent Poor Prognosticator That Enhances Cell Growth

Cited by 26 publications

References 27 publications

Inhibition of Enhancer of Zeste Homolog 2 (EZH2) Expression Is Associated With Decreased Tumor Cell Proliferation, Migration, and Invasion in Endometrial Cancer Cell Lines

Inhibition of Enhancer of Zeste Homolog 2 (EZH2) Expression Is Associated With Decreased Tumor Cell Proliferation, Migration, and Invasion in Endometrial Cancer Cell Lines

Interplay of DNA methyltransferase 1 and EZH2 through inactivation of Stat3 contributes to β-elemene-inhibited growth of nasopharyngeal carcinoma cells

Efficacy of extracts of Celastrusï¿½orbiculatus in suppressing migration and invasion by inhibiting the EZH2/ROCK1 signaling pathway in human nasopharyngeal carcinoma

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