title: Epigenetic regulation of cancer biology and anti-tumor immunity by EZH2.
abstract: Polycomb group proteins regulate chromatin structure and have an important regulatory role on gene expression in various cell types. Two polycomb group complexes (Polycomb repressive complex 1 (PRC1) and 2 (PRC2)) have been identified in mammalian cells. Both PRC1 and PRC2 compact chromatin, and also catalyze histone modifications. PRC1 mediates monoubiquitination of histone H2A, whereas PRC2 catalyzes methylation of histone H3 on lysine 27. These alterations of histones can lead to altered gene expression patterns by regulating chromatin structure. Numerous studies have highlighted the role of the PRC2 catalytic component enhancer of zeste homolog 2 (EZH2) in neoplastic development and progression, and EZH2 mutations have been identified in various malignancies. Through modulating the expression of critical genes, EZH2 is actively involved in fundamental cellular processes such as cell cycle progression, cell proliferation, differentiation and apoptosis. In addition to cancer cells, EZH2 also has a decisive role in the differentiation and function of T effector and T regulatory cells. In this review we summarize the recent progress regarding the role of EZH2 in human malignancies, highlight the molecular mechanisms by which EZH2 aberrations promote the pathogenesis of cancer, and discuss the anti-tumor effects of EZH2 targeting via activating direct anti-cancer mechanisms and anti-tumor immunity.
authors: Division of Hematology-Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA.|Department of Medicine Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors: Anthos
authors: A
authors: Christofides
authors: Division of Hematology-Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA.|Department of Medicine Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.|General Internal Medicine Section, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA.
authors: Theodoros
authors: T
authors: Karantanos
authors: Division of Hematology-Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA.|Department of Medicine Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors: Kankana
authors: K
authors: Bardhan
authors: Division of Hematology-Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA.|Department of Medicine Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors: Vassiliki A
authors: VA
authors: Boussiotis
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D042002:Chromatin Assembly and Disassembly; D019175:DNA Methylation / Q000187:drug effects; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction; D019139:Tumor Escape / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein
keywords: EZH2; cancer biology; cancer immunology; epigenetics