IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms10637.html
   My bibliography  Save this article

Downregulation of TLX induces TET3 expression and inhibits glioblastoma stem cell self-renewal and tumorigenesis

Author

Listed:
  • Qi Cui

    (Cancer Center, Beckman Research Institute of City of Hope
    Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope)

  • Su Yang

    (Cancer Center, Beckman Research Institute of City of Hope
    Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope)

  • Peng Ye

    (Cancer Center, Beckman Research Institute of City of Hope)

  • E. Tian

    (Cancer Center, Beckman Research Institute of City of Hope)

  • Guoqiang Sun

    (Cancer Center, Beckman Research Institute of City of Hope)

  • Jiehua Zhou

    (Beckman Research Institute of City of Hope)

  • Guihua Sun

    (Beckman Research Institute of City of Hope)

  • Xiaoxuan Liu

    (Aix-Marseille Université, CNRS, UMR 7325, Centre Interdisciplinaire de Nanoscience de Marseille)

  • Chao Chen

    (Aix-Marseille Université, CNRS, UMR 7325, Centre Interdisciplinaire de Nanoscience de Marseille)

  • Kiyohito Murai

    (Cancer Center, Beckman Research Institute of City of Hope)

  • Chunnian Zhao

    (Cancer Center, Beckman Research Institute of City of Hope)

  • Krist T. Azizian

    (Beckman Research Institute of City of Hope)

  • Lu Yang

    (Integrative Genomics Core, Beckman Research Institute of City of Hope)

  • Charles Warden

    (Integrative Genomics Core, Beckman Research Institute of City of Hope)

  • Xiwei Wu

    (Integrative Genomics Core, Beckman Research Institute of City of Hope)

  • Massimo D'Apuzzo

    (Beckman Research Institute of City of Hope)

  • Christine Brown

    (Beckman Research Institute of City of Hope)

  • Behnam Badie

    (Beckman Research Institute of City of Hope)

  • Ling Peng

    (Aix-Marseille Université, CNRS, UMR 7325, Centre Interdisciplinaire de Nanoscience de Marseille)

  • Arthur D. Riggs

    (Beckman Research Institute of City of Hope)

  • John J. Rossi

    (Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope
    Beckman Research Institute of City of Hope)

  • Yanhong Shi

    (Cancer Center, Beckman Research Institute of City of Hope
    Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope)

Abstract

Glioblastomas have been proposed to be maintained by highly tumorigenic glioblastoma stem cells (GSCs) that are resistant to current therapy. Therefore, targeting GSCs is critical for developing effective therapies for glioblastoma. In this study, we identify the regulatory cascade of the nuclear receptor TLX and the DNA hydroxylase Ten eleven translocation 3 (TET3) as a target for human GSCs. We show that knockdown of TLX expression inhibits human GSC tumorigenicity in mice. Treatment of human GSC-grafted mice with viral vector-delivered TLX shRNA or nanovector-delivered TLX siRNA inhibits tumour development and prolongs survival. Moreover, we identify TET3 as a potent tumour suppressor downstream of TLX to regulate the growth and self-renewal in GSCs. This study identifies the TLX-TET3 axis as a potential therapeutic target for glioblastoma.

Suggested Citation

  • Qi Cui & Su Yang & Peng Ye & E. Tian & Guoqiang Sun & Jiehua Zhou & Guihua Sun & Xiaoxuan Liu & Chao Chen & Kiyohito Murai & Chunnian Zhao & Krist T. Azizian & Lu Yang & Charles Warden & Xiwei Wu & Ma, 2016. "Downregulation of TLX induces TET3 expression and inhibits glioblastoma stem cell self-renewal and tumorigenesis," Nature Communications, Nature, vol. 7(1), pages 1-15, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10637
    DOI: 10.1038/ncomms10637
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms10637
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms10637?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:7:y:2016:i:1:d:10.1038_ncomms10637. 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.