IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms10994.html
   My bibliography  Save this article

LIG4 mediates Wnt signalling-induced radioresistance

Author

Listed:
  • Sohee Jun

    (The University of Texas MD Anderson Cancer Center)

  • Youn-Sang Jung

    (The University of Texas MD Anderson Cancer Center)

  • Han Na Suh

    (The University of Texas MD Anderson Cancer Center)

  • Wenqi Wang

    (The University of Texas MD Anderson Cancer Center)

  • Moon Jong Kim

    (The University of Texas MD Anderson Cancer Center)

  • Young Sun Oh

    (The University of Texas MD Anderson Cancer Center)

  • Esther M. Lien

    (The University of Texas MD Anderson Cancer Center)

  • Xi Shen

    (The University of Texas MD Anderson Cancer Center)

  • Yoshihisa Matsumoto

    (Research Laboratory for Nuclear Reactors, Tokyo Institute of Technology)

  • Pierre D. McCrea

    (The University of Texas MD Anderson Cancer Center
    Graduate School of Biomedical Sciences at Houston, The University of Texas Health Science Center and MD Anderson Cancer Center
    Program in Genes and Development, The University of Texas MD Anderson Cancer Center)

  • Lei Li

    (The University of Texas MD Anderson Cancer Center
    Graduate School of Biomedical Sciences at Houston, The University of Texas Health Science Center and MD Anderson Cancer Center
    Program in Genes and Development, The University of Texas MD Anderson Cancer Center)

  • Junjie Chen

    (The University of Texas MD Anderson Cancer Center
    Graduate School of Biomedical Sciences at Houston, The University of Texas Health Science Center and MD Anderson Cancer Center
    Program in Genes and Development, The University of Texas MD Anderson Cancer Center)

  • Jae-Il Park

    (The University of Texas MD Anderson Cancer Center
    Graduate School of Biomedical Sciences at Houston, The University of Texas Health Science Center and MD Anderson Cancer Center
    Program in Genes and Development, The University of Texas MD Anderson Cancer Center)

Abstract

Despite the implication of Wnt signalling in radioresistance, the underlying mechanisms are unknown. Here we find that high Wnt signalling is associated with radioresistance in colorectal cancer (CRC) cells and intestinal stem cells (ISCs). We find that LIG4, a DNA ligase in DNA double-strand break repair, is a direct target of β-catenin. Wnt signalling enhances non-homologous end-joining repair in CRC, which is mediated by LIG4 transactivated by β-catenin. During radiation-induced intestinal regeneration, LIG4 mainly expressed in the crypts is conditionally upregulated in ISCs, accompanied by Wnt/β-catenin signalling activation. Importantly, among the DNA repair genes, LIG4 is highly upregulated in human CRC cells, in correlation with β-catenin hyperactivation. Furthermore, blocking LIG4 sensitizes CRC cells to radiation. Our results reveal the molecular mechanism of Wnt signalling-induced radioresistance in CRC and ISCs, and further unveils the unexpected convergence between Wnt signalling and DNA repair pathways in tumorigenesis and tissue regeneration.

Suggested Citation

  • Sohee Jun & Youn-Sang Jung & Han Na Suh & Wenqi Wang & Moon Jong Kim & Young Sun Oh & Esther M. Lien & Xi Shen & Yoshihisa Matsumoto & Pierre D. McCrea & Lei Li & Junjie Chen & Jae-Il Park, 2016. "LIG4 mediates Wnt signalling-induced radioresistance," Nature Communications, Nature, vol. 7(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10994
    DOI: 10.1038/ncomms10994
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms10994
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms10994?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. Syed Al Atahar, 2021. "Do people displaced by development need more than financial compensation? Evidence from Bangladesh," Development Policy Review, Overseas Development Institute, vol. 39(2), pages 212-232, March.

    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_ncomms10994. 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.