IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms8122.html
   My bibliography  Save this article

C8orf4 negatively regulates self-renewal of liver cancer stem cells via suppression of NOTCH2 signalling

Author

Listed:
  • Pingping Zhu

    (School of Life Sciences, University of Science and Technology of China
    Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China)

  • Yanying Wang

    (Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China)

  • Ying Du

    (Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China)

  • Lei He

    (PLA General Hospital)

  • Guanling Huang

    (Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China
    University of Chinese Academy of Sciences)

  • Geng Zhang

    (Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China)

  • Xinlong Yan

    (Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China)

  • Zusen Fan

    (Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China
    University of Chinese Academy of Sciences)

Abstract

Liver cancer stem cells (CSCs) harbour self-renewal and differentiation properties, accounting for chemotherapy resistance and recurrence. However, the molecular mechanisms to sustain liver CSCs remain largely unknown. In this study, based on analysis of several hepatocellular carcinoma (HCC) transcriptome datasets and our experimental data, we find that C8orf4 is weakly expressed in HCC tumours and liver CSCs. C8orf4 attenuates the self-renewal capacity of liver CSCs and tumour propagation. We show that NOTCH2 is activated in liver CSCs. C8orf4 is located in the cytoplasm of HCC tumour cells and associates with the NOTCH2 intracellular domain, which impedes the nuclear translocation of N2ICD. C8orf4 deletion causes the nuclear translocation of N2ICD that triggers the NOTCH2 signalling, which sustains the stemness of liver CSCs. Finally, NOTCH2 activation levels are consistent with clinical severity and prognosis of HCC patients. Altogether, C8orf4 negatively regulates the self-renewal of liver CSCs via suppression of NOTCH2 signalling.

Suggested Citation

  • Pingping Zhu & Yanying Wang & Ying Du & Lei He & Guanling Huang & Geng Zhang & Xinlong Yan & Zusen Fan, 2015. "C8orf4 negatively regulates self-renewal of liver cancer stem cells via suppression of NOTCH2 signalling," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8122
    DOI: 10.1038/ncomms8122
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms8122
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms8122?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Zhenzhen Chen & Qiankun He & Tiankun Lu & Jiayi Wu & Gaoli Shi & Luyun He & Hong Zong & Benyu Liu & Pingping Zhu, 2023. "mcPGK1-dependent mitochondrial import of PGK1 promotes metabolic reprogramming and self-renewal of liver TICs," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

    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_ncomms8122. 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.