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

Author:

Xu Kexin12,Wu Zhenhua Jeremy13,Groner Anna C.12,He Housheng Hansen123,Cai Changmeng4,Lis Rosina T.256,Wu Xiaoqiu25,Stack Edward C.256,Loda Massimo2567,Liu Tao13,Xu Han13,Cato Laura12,Thornton James E.89,Gregory Richard I.89,Morrissey Colm10,Vessella Robert L.1011,Montironi Rodolfo12,Magi-Galluzzi Cristina13,Kantoff Philip W.2,Balk Steven P.4,Liu X. Shirley13,Brown Myles12

Affiliation:

1. Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

2. Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.

3. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, MA 02115, USA.

4. Hematology-Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.

5. Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

6. Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

7. Division of Cancer Studies, King’s College London, London SE1 8UB, UK.

8. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.

9. Stem Cell Program, Children’s Hospital, Boston, MA 02115, USA.

10. Department of Urology, University of Washington Medical Center, Seattle, WA 98195, USA.

11. Puget Sound VA Health Care System, Seattle, WA 98108, USA.

12. Section of Pathological Anatomy, Polytechnic University of Marche Region, United Hospitals, 60126 Torrette, Ancona, Italy.

13. Pathology and Laboratory Medicine Institute, Glickman Urological and Kidney Institute, Department of Cancer Biology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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