title: Multifaceted role of EZH2 in breast and prostate tumorigenesis: epigenetics and beyond.
abstract: Overexpression of EZH2 and other PRC2 subunits, such as SUZ12, is associated with tumor progression and poor prognosis in several human malignancies. Nevertheless, the underlying mechanisms driving aberrant EZH2 expression are poorly understood. This review provides molecular insights into the essential role of EZH2 in breast and prostate tumorigenesis. We addressed the current understanding on the oncogenic role of EZH2, with an emphasis on: (1) the less known PRC2-independent role of EZH2 in gene activation, in addition to its canonical role in transcriptional silencing as a histone methyltransferase catalyzing the trimethylation of histone H3 at lysine 27; (2) causes and consequences of its deregulation in tumor cells and; (3) collaboration of EZH2 with other epigenetic and hormone receptor-mediated oncogenic signaling pathways. We also summarize how EZH2 has emerged as a promising therapeutic target in hormone-refractory cancers and the prospects for integrating EZH2 blockade with available pharmacological inhibitors.
authors: Department of Urology, Case Western Reserve University, Cleveland, OH, USA.
authors: Gauri
authors: G
authors: Deb
authors: Vijay S
authors: VS
authors: Thakur
authors: Sanjay
authors: S
authors: Gupta
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics*
chemical_list: D006657:Histones; D063151:Polycomb Repressive Complex 2
keywords: EZH2; H3K27 trimethylation; PRC2 complex; androgen receptor; breast cancer; estrogen receptor; prostate cancer
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