Epigenetic regulation of cancer progression by EZH2: from biological insights to therapeutic potential

被引：302

作者：

Gan, Lu ^{[1
,2
,3
]}

Yang, Yanan ^{[1
]}

Li, Qian ^{[2
,3
]}

Feng, Yi ^{[2
,3
]}

Liu, Tianshu ^{[2
,3
]}

Guo, Weijian ^{[1
,2
]}

机构：

[1] Fudan Univ, Shanghai Canc Ctr, Dept Med Oncol, 270 Dongan Rd, Shanghai 200032, Peoples R China

[2] Fudan Univ, Dept Oncol, Shanghai Med Coll, 130 Dongan Rd, Shanghai 200032, Peoples R China

[3] Fudan Univ, Dept Med Oncol, Zhongshan Hosp, 180 Fenglin Rd, Shanghai 200032, Peoples R China

来源：

BIOMARKER RESEARCH | 2018年 / 6卷

关键词：

EZH2; Epigenetic; Histone H3 Lys27 trimethylation; Cancer; Polycomb repressive complex; HISTONE METHYLTRANSFERASE EZH2; GROUP PROTEIN EZH2; GENE-EXPRESSION; SELECTIVE INHIBITOR; SOMATIC MUTATIONS; TARGETING EZH2; CELLS; METHYLATION; PHOSPHORYLATION; PROLIFERATION;

D O I：

10.1186/s40364-018-0122-2

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and a catalytic component of PRC2, catalyzes tri-methylation of histone H3 at Lys 27 (H3K27me3) to regulate gene expression through epigenetic machinery. EZH2 also functions both as a transcriptional suppressor and a transcriptional co-activator, depending on H3K27me3 or not and on the different cellular contexts. Unsurprisingly, numerous studies have highlighted the role of EZH2 in cancer development and progression. Through modulating critical gene expression, EZH2 promotes cell survival, proliferation, epithelial to mesenchymal, invasion, and drug resistance of cancer cells. The tumor suppressive effects of EZH2 are also identified. What is more, EZH2 has decisive roles in immune cells (for example, T cells, NK cells, dendritic cells and macrophages), which are essential components in tumor microenvironment. In this review, we aim to discuss the molecular functions of EZH2, highlight recent findings regarding the physiological functions and related regulation of EZH2 in cancer pathogenesis. Furthermore, we summarized and updated the emerging roles of EZH2 in tumor immunity, and current pre-clinical and clinical trials of EZH2 inhibitors in cancer therapy.

引用

页数：10

共 98 条

[1] Three-dimensional culture sensitizes epithelial ovarian cancer cells to EZH2 methyltransferase inhibition [J].

Amatangelo, Michael D. ;

Garipov, Azat ;

Li, Hua ;

Conejo-Garcia, Jose R. ;

Speicher, David W. ;

Zhang, Rugang .

CELL CYCLE, 2013, 12 (13) :2113-2119

[2]

[Anonymous], CANC RES

[3] EZH2 Is Required for Germinal Center Formation and Somatic EZH2 Mutations Promote Lymphoid Transformation [J].

Beguelin, Wendy ;

Popovic, Relja ;

Teater, Matt ;

Jiang, Yanwen ;

Bunting, Karen L. ;

Rosen, Monica ;

Shen, Hao ;

Yang, Shao Ning ;

Wang, Ling ;

Ezponda, Teresa ;

Martinez-Garcia, Eva ;

Zhang, Haikuo ;

Zheng, Yupeng ;

Verma, Sharad K. ;

McCabe, Michael T. ;

Ott, Heidi M. ;

Van Aller, Glenn S. ;

Kruger, Ryan G. ;

Liu, Yan ;

McHugh, Charles F. ;

Scott, David W. ;

Chung, Young Rock ;

Kelleher, Neil ;

Shaknovich, Rita ;

Creasy, Caretha L. ;

Gascoyne, Randy D. ;

Wong, Kwok-Kin ;

Cerchietti, Leandro ;

Levine, Ross L. ;

Abdel-Wahab, Omar ;

Licht, Jonathan D. ;

Elemento, Olivier ;

Melnick, Ari M. .

CANCER CELL, 2013, 23 (05) :677-692

[4] EZH2 Y641 mutations in follicular lymphoma [J].

Boedoer, C. ;

O'Riain, C. ;

Wrench, D. ;

Matthews, J. ;

Iyengar, S. ;

Tayyib, H. ;

Calaminici, M. ;

Clear, A. ;

Iqbal, S. ;

Quentmeier, H. ;

Drexler, H. G. ;

Montoto, S. ;

Lister, A. T. ;

Gribben, J. G. ;

Matolcsy, A. ;

Fitzgibbon, J. .

LEUKEMIA, 2011, 25 (04) :726-729

[5] EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer [J].

Adrian P. Bracken ;

Diego Pasini ;

Maria Capra ;

Elena Prosperini ;

Elena Colli ;

Kristian Helin .

The EMBO Journal, 2003, 22 (20) :5323-5335

[6] EPZ011989, A Potent, Orally-Available EZH2 Inhibitor with Robust in Vivo Activity [J].

Campbell, John E. ;

Kuntz, Kevin W. ;

Knutson, Sarah K. ;

Warholic, Natalie M. ;

Keilhack, Heike ;

Wigle, Tim J. ;

Raimondi, Alejandra ;

Klaus, Christine R. ;

Rioux, Nathalie ;

Yokoi, Akira ;

Kawano, Satoshi ;

Minoshima, Yukinori ;

Choi, Hyeong-Wook ;

Scott, Margaret Porter ;

Waters, Nigel J. ;

Smith, Jesse J. ;

Chesworth, Richard ;

Moyer, Mikel P. ;

Copeland, Robert A. .

ACS MEDICINAL CHEMISTRY LETTERS, 2015, 6 (05) :491-495

[7] Repression of E-cadherin by the polycomb group protein EZH2 in cancer [J].

Cao, Q. ;

Yu, J. ;

Dhanasekaran, S. M. ;

Kim, J. H. ;

Mani, R-S ;

Tomlins, S. A. ;

Mehra, R. ;

Laxman, B. ;

Cao, X. ;

Yu, J. ;

Kleer, C. G. ;

Varambally, S. ;

Chinnaiyan, A. M. .

ONCOGENE, 2008, 27 (58) :7274-7284

[8] The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3 [J].

Cao, R ;

Zhang, Y .

CURRENT OPINION IN GENETICS & DEVELOPMENT, 2004, 14 (02) :155-164

[9] EZH2 is associated with poor prognosis in head-and-neck squamous cell carcinoma via regulating the epithelial-to-mesenchymal transition and chemosensitivity [J].

Chang, Jae Won ;

Gwak, Seo Young ;

Shim, Geun-Ae ;

Liu, Lihua ;

Lim, Young Chang ;

Kim, Jin Man ;

Jung, Min Gyu ;

Koo, Bon Seok .

ORAL ONCOLOGY, 2016, 52 :66-74

[10] EZH2 Palmitoylation Mediated by ZDHHC5 in p53-Mutant Glioma Drives Malignant Development and Progression [J].

Chen, Xueran ;

Ma, Huihui ;

Wang, Zhen ;

Zhang, Shangrong ;

Yang, Haoran ;

Fang, Zhiyou .

CANCER RESEARCH, 2017, 77 (18) :4998-5010

← 1 2 3 4 5 6 7 8 9 10 →