Polycomb group proteins EZH2 and EED directly regulate androgen receptor in advanced prostate cancer

Qipeng Liu, Guangyu Wang, Qiaqia Li, Weihua Jiang, Jung Sun Kim, Rui Wang, Sen Zhu, Xiaoju Wang, Lin Yan, Yang Yi, Lili Zhang, Qingshu Meng, Chao Li, Dongyu Zhao, Yuanyuan Qiao, Yong Li, Demirkan Besim Gursel, Arul M. Chinnaiyan, Kaifu Chen*, Qi Cao

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Polycomb group proteins are important epigenetic regulators for cell proliferation and differentiation, organ development, as well as initiation and progression of lethal diseases, including cancer. Upregulated Polycomb group proteins, including Enhancer of zeste homolog 2 (EZH2), promote proliferation, migration, invasion and metastasis of cancer cells, as well as self-renewal of cancer stem cells. In our study, we report that EZH2 and embryonic ectoderm development (EED) indicate respective direct interaction with androgen receptor (AR). In the context of AR-positive prostate cancer, EZH2 and EED regulate AR expression levels and AR downstream targets. More importantly, we demonstrate that targeting EZH2 with the small-molecule inhibitor astemizole in cancer significantly represses the EZH2 and AR expression as well as the neoplastic capacities. These results collectively suggest that pharmacologically targeting EZH2 might be a promising strategy for advanced prostate cancer.

Original languageEnglish (US)
Pages (from-to)415-426
Number of pages12
JournalInternational Journal of Cancer
Volume145
Issue number2
DOIs
StatePublished - Jul 15 2019

Fingerprint

Polycomb-Group Proteins
Ectoderm
Androgen Receptors
Embryonic Development
Prostatic Neoplasms
Astemizole
Neoplasms
Neoplastic Stem Cells
Epigenomics
Disease Progression
Enhancer of Zeste Homolog 2 Protein
Cell Differentiation
Cell Proliferation
Neoplasm Metastasis

Keywords

  • EED
  • EZH2
  • androgen receptor
  • astemizole
  • prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Liu, Qipeng ; Wang, Guangyu ; Li, Qiaqia ; Jiang, Weihua ; Kim, Jung Sun ; Wang, Rui ; Zhu, Sen ; Wang, Xiaoju ; Yan, Lin ; Yi, Yang ; Zhang, Lili ; Meng, Qingshu ; Li, Chao ; Zhao, Dongyu ; Qiao, Yuanyuan ; Li, Yong ; Gursel, Demirkan Besim ; Chinnaiyan, Arul M. ; Chen, Kaifu ; Cao, Qi. / Polycomb group proteins EZH2 and EED directly regulate androgen receptor in advanced prostate cancer. In: International Journal of Cancer. 2019 ; Vol. 145, No. 2. pp. 415-426.
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abstract = "Polycomb group proteins are important epigenetic regulators for cell proliferation and differentiation, organ development, as well as initiation and progression of lethal diseases, including cancer. Upregulated Polycomb group proteins, including Enhancer of zeste homolog 2 (EZH2), promote proliferation, migration, invasion and metastasis of cancer cells, as well as self-renewal of cancer stem cells. In our study, we report that EZH2 and embryonic ectoderm development (EED) indicate respective direct interaction with androgen receptor (AR). In the context of AR-positive prostate cancer, EZH2 and EED regulate AR expression levels and AR downstream targets. More importantly, we demonstrate that targeting EZH2 with the small-molecule inhibitor astemizole in cancer significantly represses the EZH2 and AR expression as well as the neoplastic capacities. These results collectively suggest that pharmacologically targeting EZH2 might be a promising strategy for advanced prostate cancer.",
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author = "Qipeng Liu and Guangyu Wang and Qiaqia Li and Weihua Jiang and Kim, {Jung Sun} and Rui Wang and Sen Zhu and Xiaoju Wang and Lin Yan and Yang Yi and Lili Zhang and Qingshu Meng and Chao Li and Dongyu Zhao and Yuanyuan Qiao and Yong Li and Gursel, {Demirkan Besim} and Chinnaiyan, {Arul M.} and Kaifu Chen and Qi Cao",
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Liu, Q, Wang, G, Li, Q, Jiang, W, Kim, JS, Wang, R, Zhu, S, Wang, X, Yan, L, Yi, Y, Zhang, L, Meng, Q, Li, C, Zhao, D, Qiao, Y, Li, Y, Gursel, DB, Chinnaiyan, AM, Chen, K & Cao, Q 2019, 'Polycomb group proteins EZH2 and EED directly regulate androgen receptor in advanced prostate cancer', International Journal of Cancer, vol. 145, no. 2, pp. 415-426. https://doi.org/10.1002/ijc.32118

Polycomb group proteins EZH2 and EED directly regulate androgen receptor in advanced prostate cancer. / Liu, Qipeng; Wang, Guangyu; Li, Qiaqia; Jiang, Weihua; Kim, Jung Sun; Wang, Rui; Zhu, Sen; Wang, Xiaoju; Yan, Lin; Yi, Yang; Zhang, Lili; Meng, Qingshu; Li, Chao; Zhao, Dongyu; Qiao, Yuanyuan; Li, Yong; Gursel, Demirkan Besim; Chinnaiyan, Arul M.; Chen, Kaifu; Cao, Qi.

In: International Journal of Cancer, Vol. 145, No. 2, 15.07.2019, p. 415-426.

Research output: Contribution to journalArticle

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T1 - Polycomb group proteins EZH2 and EED directly regulate androgen receptor in advanced prostate cancer

AU - Liu, Qipeng

AU - Wang, Guangyu

AU - Li, Qiaqia

AU - Jiang, Weihua

AU - Kim, Jung Sun

AU - Wang, Rui

AU - Zhu, Sen

AU - Wang, Xiaoju

AU - Yan, Lin

AU - Yi, Yang

AU - Zhang, Lili

AU - Meng, Qingshu

AU - Li, Chao

AU - Zhao, Dongyu

AU - Qiao, Yuanyuan

AU - Li, Yong

AU - Gursel, Demirkan Besim

AU - Chinnaiyan, Arul M.

AU - Chen, Kaifu

AU - Cao, Qi

PY - 2019/7/15

Y1 - 2019/7/15

N2 - Polycomb group proteins are important epigenetic regulators for cell proliferation and differentiation, organ development, as well as initiation and progression of lethal diseases, including cancer. Upregulated Polycomb group proteins, including Enhancer of zeste homolog 2 (EZH2), promote proliferation, migration, invasion and metastasis of cancer cells, as well as self-renewal of cancer stem cells. In our study, we report that EZH2 and embryonic ectoderm development (EED) indicate respective direct interaction with androgen receptor (AR). In the context of AR-positive prostate cancer, EZH2 and EED regulate AR expression levels and AR downstream targets. More importantly, we demonstrate that targeting EZH2 with the small-molecule inhibitor astemizole in cancer significantly represses the EZH2 and AR expression as well as the neoplastic capacities. These results collectively suggest that pharmacologically targeting EZH2 might be a promising strategy for advanced prostate cancer.

AB - Polycomb group proteins are important epigenetic regulators for cell proliferation and differentiation, organ development, as well as initiation and progression of lethal diseases, including cancer. Upregulated Polycomb group proteins, including Enhancer of zeste homolog 2 (EZH2), promote proliferation, migration, invasion and metastasis of cancer cells, as well as self-renewal of cancer stem cells. In our study, we report that EZH2 and embryonic ectoderm development (EED) indicate respective direct interaction with androgen receptor (AR). In the context of AR-positive prostate cancer, EZH2 and EED regulate AR expression levels and AR downstream targets. More importantly, we demonstrate that targeting EZH2 with the small-molecule inhibitor astemizole in cancer significantly represses the EZH2 and AR expression as well as the neoplastic capacities. These results collectively suggest that pharmacologically targeting EZH2 might be a promising strategy for advanced prostate cancer.

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