Multifaceted role of EZH2 in breast and prostate tumorigenesis

Deb, Gauri; Thakur, Vijay S.; Gupta, Sanjay

doi:10.4161/epi.24532

Cited by 72 publications

(73 citation statements)

References 132 publications

(154 reference statements)

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“…reported that increased expression of polycomb group protein EZH2 in metastatic prostate tumor samples distinguished them from organ-confined localized tumors (61). EZH2 has been found to promote prostate carcinogenesis by PRC2-mediated silencing of critical tumor suppressor genes such as DAB2IP , SLIT2 , TIMP-3 , and MSMB [reviewed in (37)]. However a recent study by Xu et al .…”

Section: Role Of Ezh2 In Cancer Progressionmentioning

confidence: 99%

“…In prostate cancer, various molecular mechanisms have been proposed to be responsible for EZH2 over-expression which includes EZH2 gene amplification, miR-101 deletion, and transcriptional regulation by MYC and ETS gene family members [reviewed in (37)]. Using fluorescence in situ hybridization technique, Saramaki and colleagues determined the copy number of EZH2 gene in prostate cancer cell lines LNCaP, DU145, PC-3, 22Rv1, xenografts and clinical tumors (64).…”

Section: Role Of Ezh2 In Cancer Progressionmentioning

confidence: 99%

“…In our previous review, we have comprehensively discussed the mechanism of action of EZH2 as a transcriptional inducer, where it functions independently (not as part of PRC2 complex), in endocrine-related cancers of the breast and prostate [reviewed in (37)]. Depending on the estrogen receptor (ER) status of the breast cancer cells, the EZH2 mediated target gene activation mechanism varies.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Role Of Ezh2 In Cancer Progressionmentioning

confidence: 99%

Section: Role Of Ezh2 In Cancer Progressionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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EZH2: Not EZHY (Easy) to Deal

Deb

Singh

Gupta

2014

Molecular Cancer Research

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“…EZH2 has been reported to be of both prognostic and therapeutic value in different tumors, such as small cell lung carcinoma [70], breast cancer [71, 72], cervical carcinomas [73], urinary tract carcinoma [74], and lymphoma [75]. Through gene expression profiling, EZH2 was found to be overexpressed in hormone-refractory metastatic prostate cancer [69].…”

Section: Molecular Markersmentioning

confidence: 99%

Prognostic Histopathological and Molecular Markers on Prostate Cancer Needle-Biopsies: A Review

Hoogland

Kweldam

Leenders

2014

BioMed Research International

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Prostate cancer is diverse in clinical presentation, histopathological tumor growth patterns, and survival. Therefore, individual assessment of a tumor's aggressive potential is crucial for clinical decision-making in men with prostate cancer. To date a large number of prognostic markers for prostate cancer have been described, most of them based on radical prostatectomy specimens. However, in order to affect clinical decision-making, validation of respective markers in pretreatment diagnostic needle-biopsies is essential. Here, we discuss established and promising histopathological and molecular parameters in diagnostic needle-biopsies.

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“…The upregulation of this polycomb-associated methyltransferase, which specifically methylates H3K27, may be of some significance in pheochromocytoma tumorigenesis as it may contribute to silencing tumor suppressor genes (Sandgren et al 2010). Furthermore, EZH2 overexpression has also been observed in other cancer types (Deb et al 2013).…”

Section: Ovarian Cancer Stromal Tumors (Frequency !3%)mentioning

confidence: 99%

Epigenetic alterations in endocrine-related cancer

Rodríguez-Rodero¹,

Delgado²,

Fernández³

et al. 2014

Endocrine-Related Cancer

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Aberrant epigenetics is a hallmark of cancer, and endocrine-related tumors are no exception. Recent research has been identifying an ever-growing number of epigenetic alterations in both genomic DNA methylation and histone post-translational modification in tumors of the endocrine system. Novel microarray and ultra-deep sequencing technologies have allowed the identification of genome-wide epigenetic patterns in some tumor types such as adrenocortical, parathyroid, and breast carcinomas. However, in other cancer types, such as the multiple endocrine neoplasia syndromes and thyroid cancer, tumor information is limited to candidate genes alone. Future research should fill this gap and deepen our understanding of the functional role of these alterations in cancer, as well as defining their possible clinical uses.

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Multifaceted role of EZH2 in breast and prostate tumorigenesis

Cited by 72 publications

References 132 publications

EZH2: Not EZHY (Easy) to Deal

EZH2: Not EZHY (Easy) to Deal

Prognostic Histopathological and Molecular Markers on Prostate Cancer Needle-Biopsies: A Review

Epigenetic alterations in endocrine-related cancer

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