EZH2 Oncogenic Activity in Castration-Resistant Prostate Cancer Cells Is Polycomb-Independent

American Association for the Advancement of Science (AAAS) - Tập 338 Số 6113 - Trang 1465-1469 - 2012
Kexin Xu1,1, Zhenhua J. Wu2,2, Anna C. Groner1,1, Housheng Hansen He2,1, Changmeng Cai3, Rosina T. Lis4,1,5, Xiaoqiu Wu4,1, Edward C. Stack4,1,5, Massimo Loda4,1,5,6, Tao Liu2,2, Han Xu2,2, Laura Cato1,1, James E. Thornton7,8, Richard I. Gregory7,8, Colm Morrissey9, Robert L. Vessella9,10, Rodolfo Montironi11, Cristina Magi‐Galluzzi12, Philip W. Kantoff1, Steven P. Balk3, X. Shirley Liu2,2, Myles Brown1,1
1Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
2Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, MA 02115, USA
3Hematology-Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
4Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
5Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
6Division of Cancer Studies, King’s College London, London SE1 8UB, UK.
7Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
8Stem Cell Program, Children's Hospital, Boston, MA 02115, USA
9Department of Urology, University of Washington Medical Center, Seattle, WA 98195, USA.
10Puget Sound VA Health Care System, Seattle, WA 98108, USA.
11Section of Pathological Anatomy, Polytechnic University of Marche Region, United Hospitals, 60126 Torrette, Ancona, Italy.
12Pathology and Laboratory Medicine Institute, Glickman Urological and Kidney Institute, Department of Cancer Biology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

Tóm tắt

Alternative Role for EZH2 Epigenetic regulators are implicated in cancer progression and proposed as therapeutic targets. Xu et al. (p. 1465 ; see the Perspective by Cavalli ) report that EZH2 (Enhancer of zeste homolog 2), a factor previously thought to exert its oncogenic function primarily as part of the polycomb repressive complex, acts through a distinct mechanism in cells of castration-resistant prostate cancer. Rather than exclusively silencing gene expression through histone methylation, EZH2 acts as a transcriptional coactivator. The activation function of EZH2 plays a critical role in the growth of castration-resistant prostate cancer cells, which could be relevant in future drug development.

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