IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-02863-3.html
   My bibliography  Save this article

BMI1 regulates androgen receptor in prostate cancer independently of the polycomb repressive complex 1

Author

Listed:
  • Sen Zhu

    (Houston Methodist Research Institute)

  • Dongyu Zhao

    (Houston Methodist Research Institute
    Cornell University)

  • Lin Yan

    (Houston Methodist Research Institute
    Central South University)

  • Weihua Jiang

    (Houston Methodist Research Institute)

  • Jung-Sun Kim

    (Houston Methodist Research Institute)

  • Bingnan Gu

    (Houston Methodist Research Institute)

  • Qipeng Liu

    (Houston Methodist Research Institute
    Central South University)

  • Rui Wang

    (Houston Methodist Research Institute)

  • Bo Xia

    (Houston Methodist Research Institute
    Cornell University)

  • Jonathan C. Zhao

    (Northwestern University Feinberg School of Medicine)

  • Gang Song

    (Peking University)

  • Wenyi Mi

    (The University of Texas MD Anderson Cancer Center)

  • Rong-Fu Wang

    (Houston Methodist Research Institute
    Cornell University)

  • Xiaobing Shi

    (The University of Texas MD Anderson Cancer Center)

  • Hung-Ming Lam

    (University of Washington
    Macau University of Science and Technology)

  • Xuesen Dong

    (Vancouver Prostate Centre, Vancouver General Hospital
    University of British Columbia)

  • Jindan Yu

    (Northwestern University Feinberg School of Medicine
    Northwestern University Feinberg School of Medicine)

  • Kaifu Chen

    (Houston Methodist Research Institute
    Cornell University)

  • Qi Cao

    (Houston Methodist Research Institute
    Cornell University
    Houston Methodist Research Institute)

Abstract

BMI1, a polycomb group (PcG) protein, plays a critical role in epigenetic regulation of cell differentiation and proliferation, and cancer stem cell self-renewal. BMI1 is upregulated in multiple types of cancer, including prostate cancer. As a key component of polycomb repressive complex 1 (PRC1), BMI1 exerts its oncogenic functions by enhancing the enzymatic activities of RING1B to ubiquitinate histone H2A at lysine 119 and repress gene transcription. Here, we report a PRC1-independent role of BMI1 that is critical for castration-resistant prostate cancer (CRPC) progression. BMI1 binds the androgen receptor (AR) and prevents MDM2-mediated AR protein degradation, resulting in sustained AR signaling in prostate cancer cells. More importantly, we demonstrate that targeting BMI1 effectively inhibits tumor growth of xenografts that have developed resistance to surgical castration and enzalutamide treatment. These results suggest that blocking BMI1 alone or in combination with anti-AR therapy can be more efficient to suppress prostate tumor growth.

Suggested Citation

  • Sen Zhu & Dongyu Zhao & Lin Yan & Weihua Jiang & Jung-Sun Kim & Bingnan Gu & Qipeng Liu & Rui Wang & Bo Xia & Jonathan C. Zhao & Gang Song & Wenyi Mi & Rong-Fu Wang & Xiaobing Shi & Hung-Ming Lam & Xu, 2018. "BMI1 regulates androgen receptor in prostate cancer independently of the polycomb repressive complex 1," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-02863-3
    DOI: 10.1038/s41467-018-02863-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-02863-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-02863-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-02863-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.