Aberrant expression of EZH2 is associated with a poor outcome and P53 alteration in squamous cell carcinoma of the esophagus

Yamada, Atsushi; Fujii, Satoshi; Daiko, Hiroyuki; Nishimura, Mitsuyo; Chiba, Tsutomu; Ochiai, Atsushi

doi:10.3892/ijo.2010.868

Cited by 29 publications

(21 citation statements)

References 39 publications

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“…Elevated EZH2 was significantly correlated with TNM stage and lymph node metastasis in CRC tissues [13]. Moreover, many works demonstrate that upregulation of EZH2 is a sign of poor prognosis [10,11,12], which indicate that EZH2 as an oncogene. However, there is disparate point of view that high level expression of EZH2 inhibits aggressive T-acute lymphoblastic leukemia [18], which means EZH2 can also act as a tumor suppressor.…”

Section: Discussionmentioning

confidence: 99%

“…Increasing evidence indicates that EZH2 is associated with a number of cancers, including nasopharyngeal esophageal cancer, breast cancer, lung cancer and bladder cancer [6,7,8,9]. Moreover, overexpression of EZH2 indicates the tumor more aggressive and is related to poor prognosis [10,11,12]. In our previous immunohistochemical research, we found that expression of the EZH2 was significantly higher in tumor tissues than the paired normal tissues, and EZH2 might facilitate tumorigenesis in CRC cells [13].…”

Section: Introductionmentioning

confidence: 99%

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Downregulation of Enhancer of Zeste Homolog 2 (EZH2) is essential for the Induction of Autophagy and Apoptosis in Colorectal Cancer Cells

Yao

Yang

et al. 2016

Genes

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Increasing evidence indicates that elevated expression of enhancer of zeste homolog 2 gene (EZH2) in many human malignant tumors acts a significant role in the oncogenic process. However, the underlying molecular mechanism is still unclarified. It is evident that apoptosis and autophagy of tumor cells is crucial for the tumorigenesis and progression of cancer, however, the exact role of EZH2 plays in apoptosis and autophagy has not been fully elucidated in colorectal cancer (CRC). Our previous study found that the expression level of EZH2 was higher in CRC tumor tissues than in the paired normal tissues using immunohistochemical analysis. We also recently found that the autophagy-related gene-related protein Ambra1 plays an important role in the autophagy pathway in CRC cells. In this study, mRNA and protein expression of EZH2 in four CRC cell lines were tested at first and RKO and HCT116 cells showed the highest levels among them. Here we transfected with EZH2-shRNA, or added DZNep (an EZH2 inhibitor) to RKO and HCT116 cells in order to detect the effect of EZH2 on autophagy via determining the change of the protein expression of LC3 and Ambra1. The outcome indicated an obvious decrease of autophagy level in cells transfected with EZH2-shRNA or DZNep. We also found the apoptotic rate of cells was elevated significantly after downregulation of EZH2. In addition, compared to control group, CRC cells transfected with EZH2-shRNA or added DZNep revealed a significantly increased G1 cell cycle rate and an obvious decrease in the G2 cell cycle rate. Further analysis showed that knockdown of EZH2 induced cell-cycle arrest in CRC cells. Meanwhile, downregulation of EZH2 in CRC cells induces autophagy and apoptosis. Taken together, our results suggest that EZH2 plays a critical role in autophagy and apoptosis in the progression of CRC, which potentially facilitates the development of an ideal strategy for combating colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Downregulation of Enhancer of Zeste Homolog 2 (EZH2) is essential for the Induction of Autophagy and Apoptosis in Colorectal Cancer Cells

Yao

Yang

et al. 2016

Genes

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“…In fact, Yamada et al . showed that in squamous cell carcinoma of the esophagus (SCCE), elevated EZH2 expression was associated with p53 alteration and activated p53 reduced EZH2 mRNA levels in SCCE cell lines (94). Furthermore, EZH2 was found to be a miR-144 target gene and miR-144 down-regulation in bladder cancer cells was demonstrated to restore EZH2 expression, which further resulted in the activation of Wnt/ β-Catenin pathway and subsequent cell proliferation (95).…”

Section: Role Of Ezh2 In Cancer Progressionmentioning

confidence: 99%

EZH2: Not EZHY (Easy) to Deal

Deb

Singh

Gupta

2014

Molecular Cancer Research

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Seminal discoveries have established that epigenetic modifications are important for driving tumor progression. Polycomb group (PcG) proteins are highly conserved epigenetic effectors that maintain, by post-translational modification of histones, the silenced state of genes involved in critical biological processes including cellular development, stem cell plasticity and tumor progression. PcG proteins are found in two multimeric protein complexes called Polycomb Repressive Complexes: PRC1 and PRC2. Enhancer of zeste homolog 2 (EZH2), catalytic core subunit of PRC2, epigenetically silences several tumor suppressor genes by catalyzing the trimethylation of histone H3 at lysine 27, which serves as a docking site for DNA methyltransferases and histone deacetylases. Evidence suggests that over-expression of EZH2 is strongly associated with cancer progression and poor outcome in disparate cancers including hematological and epithelial malignancies. The regulatory circuit and molecular cues causing EZH2 deregulation vary in different cancer types. Therefore, this review provides a comprehensive overview on the oncogenic role of EZH2 during tumorigenesis and highlights the multi-faceted role of EZH2, as either a transcriptional activator or repressor depending on the cellular context. Additional insight is provided on the recent understanding of the causes and consequences of EZH2 over-expression in specific cancer types. Finally, evidence is discussed on how EZH2 has emerged as a promising target in anticancer therapy and the prospects for targeting EZH2 without affecting global methylation status. Thus, a better understanding of the complex epigenetic regulatory network controlling EZH2 expression and target genes facilitates the design of novel therapeutic interventions.

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“…SUZ12 and EZH2 are components of the PRC2 complex responsible for the methylation of histone 3 lysines 9 and 27 (H3K9me3 and H3K27me3). Increased expression of EZH2 has been associated with poor outcome in breast cancer [3,106-110]. As mentioned above, the PcG family of proteins plays important roles in the regulation of differentiation-related genes and may be involved in the recruitment of DNMTs [111].…”

Section: Variant Human Mammary Epithelial Cells Display Cancer-associmentioning

confidence: 99%

Epigenome remodelling in breast cancer: insights from an early in vitro model of carcinogenesis

Locke

Clark

2012

Breast Cancer Res

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Epigenetic gene regulation has influence over a diverse range of cellular functions, including the maintenance of pluripotency, differentiation, and cellular identity, and is deregulated in many diseases, including cancer. Whereas the involvement of epigenetic dysregulation in cancer is well documented, much of the mechanistic detail involved in triggering these changes remains unclear. In the current age of genomics, the development of new sequencing technologies has seen an influx of genomic and epigenomic data and drastic improvements in both resolution and coverage. Studies in cancer cell lines and clinical samples using next-generation sequencing are rapidly delivering spectacular insights into the nature of the cancer genome and epigenome. Despite these improvements in technology, the timing and relationship between genetic and epigenetic changes that occur during the process of carcinogenesis are still unclear. In particular, what changes to the epigenome are playing a driving role during carcinogenesis and what influence the temporal nature of these changes has on cancer progression are not known. Understanding the early epigenetic changes driving breast cancer has the exciting potential to provide a novel set of therapeutic targets or early-disease biomarkers or both. Therefore, it is important to find novel systems that permit the study of initial epigenetic events that potentially occur during the first stages of breast cancer. Non-malignant human mammary epithelial cells (HMECs) provide an exciting in vitro model of very early breast carcinogenesis. When grown in culture, HMECs are able to temporarily escape senescence and acquire a pre-malignant breast cancer-like phenotype (variant HMECs, or vHMECs). Cultured HMECs are composed mainly of cells from the basal breast epithelial layer. Therefore, vHMECs are considered to represent the basal-like subtype of breast cancer. The transition from HMECs to vHMECs in culture recapitulates the epigenomic phenomena that occur during the progression from normal breast to pre-malignancy. Therefore, the HMEC model system provides the unique opportunity to study the very earliest epigenomic aberrations occurring during breast carcinogenesis and can give insight into the sequence of epigenomic events that lead to breast malignancy. This review provides an overview of epigenomic research in breast cancer and discusses in detail the utility of the HMEC model system to discover early epigenomic changes involved in breast carcinogenesis.

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Aberrant expression of EZH2 is associated with a poor outcome and P53 alteration in squamous cell carcinoma of the esophagus

Cited by 29 publications

References 39 publications

Downregulation of Enhancer of Zeste Homolog 2 (EZH2) is essential for the Induction of Autophagy and Apoptosis in Colorectal Cancer Cells

Downregulation of Enhancer of Zeste Homolog 2 (EZH2) is essential for the Induction of Autophagy and Apoptosis in Colorectal Cancer Cells

EZH2: Not EZHY (Easy) to Deal

Epigenome remodelling in breast cancer: insights from an early in vitro model of carcinogenesis

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