IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-14698-y.html
   My bibliography  Save this article

Inflammation mobilizes copper metabolism to promote colon tumorigenesis via an IL-17-STEAP4-XIAP axis

Author

Listed:
  • Yun Liao

    (Cleveland Clinic
    Sichuan University)

  • Junjie Zhao

    (Cleveland Clinic)

  • Katarzyna Bulek

    (Cleveland Clinic
    Jagiellonian University)

  • Fangqiang Tang

    (Cleveland Clinic)

  • Xing Chen

    (Cleveland Clinic)

  • Gang Cai

    (Cleveland Clinic)

  • Shang Jia

    (University of California)

  • Paul L. Fox

    (Cleveland Clinic)

  • Emina Huang

    (Cleveland Clinic)

  • Theresa T. Pizarro

    (Case Western Reserve University)

  • Matthew F. Kalady

    (Cleveland Clinic)

  • Mark W. Jackson

    (Case Western Reserve University)

  • Shideng Bao

    (Cleveland Clinic)

  • Ganes C. Sen

    (Cleveland Clinic)

  • George R. Stark

    (Cleveland Clinic)

  • Christopher J. Chang

    (University of California
    University of California)

  • Xiaoxia Li

    (Cleveland Clinic)

Abstract

Copper levels are known to be elevated in inflamed and malignant tissues. But the mechanism underlying this selective enrichment has been elusive. In this study, we report a axis by which inflammatory cytokines, such as IL-17, drive cellular copper uptake via the induction of a metalloreductase, STEAP4. IL-17-induced elevated intracellular copper level leads to the activation of an E3-ligase, XIAP, which potentiates IL-17-induced NFκB activation and suppresses the caspase 3 activity. Importantly, this IL-17-induced STEAP4-dependent cellular copper uptake is critical for colon tumor formation in a murine model of colitis-associated tumorigenesis and STEAP4 expression correlates with IL-17 level and XIAP activation in human colon cancer. In summary, this study reveals a IL-17-STEAP4-XIAP axis through which the inflammatory response induces copper uptake, promoting colon tumorigenesis.

Suggested Citation

  • Yun Liao & Junjie Zhao & Katarzyna Bulek & Fangqiang Tang & Xing Chen & Gang Cai & Shang Jia & Paul L. Fox & Emina Huang & Theresa T. Pizarro & Matthew F. Kalady & Mark W. Jackson & Shideng Bao & Gane, 2020. "Inflammation mobilizes copper metabolism to promote colon tumorigenesis via an IL-17-STEAP4-XIAP axis," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14698-y
    DOI: 10.1038/s41467-020-14698-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-14698-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-14698-y?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:11:y:2020:i:1:d:10.1038_s41467-020-14698-y. 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.