IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms9126.html
   My bibliography  Save this article

YAP1 and AR interactions contribute to the switch from androgen-dependent to castration-resistant growth in prostate cancer

Author

Listed:
  • Gamze Kuser-Abali

    (Cancer Biology and Uro-Oncology Programs, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center)

  • Ahmet Alptekin

    (Cancer Biology and Uro-Oncology Programs, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center)

  • Michael Lewis

    (West Los Angeles Veteran Affairs Healthcare System)

  • Isla P. Garraway

    (West Los Angeles Veteran Affairs Healthcare System
    David Geffen School of Medicine, University of California Los Angeles
    Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California)

  • Bekir Cinar

    (Cancer Biology and Uro-Oncology Programs, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center
    West Los Angeles Veteran Affairs Healthcare System
    David Geffen School of Medicine, University of California Los Angeles
    Clark Atlanta University)

Abstract

The transcriptional co-activator Yes-associated protein 1 (YAP1), a key nuclear effector of the Hippo pathway, is a potent oncogene, and yet, the interaction between YAP1 and androgen receptor (AR) remains unexplored. Here we identify YAP1 as a physiological binding partner and positive regulator of AR in prostate cancer. YAP1 and AR co-localize and interact with each other predominantly within cell nuclei by an androgen-dependent mechanism in a hormone naive and an androgen-independent mechanism in castration-resistant prostate cancer cells. The growth suppressor MST1 kinase modulates androgen-dependent and -independent nuclear YAP1–AR interactions through directly regulating YAP1 nuclear accumulation. Disruption of YAP1 signalling by genetic (RNAi) and pharmacological (Verteporfin) approaches suppresses AR-dependent gene expression and prostate cancer cell growth. These findings indicate that the YAP1–AR axis may have a critical role in prostate cancer progression and serves as a viable drug target.

Suggested Citation

  • Gamze Kuser-Abali & Ahmet Alptekin & Michael Lewis & Isla P. Garraway & Bekir Cinar, 2015. "YAP1 and AR interactions contribute to the switch from androgen-dependent to castration-resistant growth in prostate cancer," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9126
    DOI: 10.1038/ncomms9126
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms9126
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms9126?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:6:y:2015:i:1:d:10.1038_ncomms9126. 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.