IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v478y2011i7368d10.1038_nature10491.html
   My bibliography  Save this article

An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor

Author

Listed:
  • Christiane A. Opitz

    (Neurology Clinic and National Center for Tumor Diseases University Hospital of Heidelberg
    Experimental Neuroimmunology Unit, German Cancer Research Center (DKFZ))

  • Ulrike M. Litzenburger

    (Neurology Clinic and National Center for Tumor Diseases University Hospital of Heidelberg
    Experimental Neuroimmunology Unit, German Cancer Research Center (DKFZ))

  • Felix Sahm

    (Institute of Pathology, University Hospital of Heidelberg and Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ))

  • Martina Ott

    (Neurology Clinic and National Center for Tumor Diseases University Hospital of Heidelberg
    Experimental Neuroimmunology Unit, German Cancer Research Center (DKFZ))

  • Isabel Tritschler

    (University Hospital Zurich)

  • Saskia Trump

    (Helmholtz Center for Environmental Research)

  • Theresa Schumacher

    (Neurology Clinic and National Center for Tumor Diseases University Hospital of Heidelberg
    Experimental Neuroimmunology Unit, German Cancer Research Center (DKFZ))

  • Leonie Jestaedt

    (University Hospital of Heidelberg)

  • Dieter Schrenk

    (Food Chemistry and Toxicology, University of Kaiserslautern)

  • Michael Weller

    (University Hospital Zurich)

  • Manfred Jugold

    (Small Animal Imaging Center, German Cancer Research Center (DKFZ))

  • Gilles J. Guillemin

    (School of Medical Sciences, University of New South Wales)

  • Christine L. Miller

    (Johns Hopkins University)

  • Christian Lutz

    (Heidelberg Pharma AG)

  • Bernhard Radlwimmer

    (German Cancer Research Center (DKFZ))

  • Irina Lehmann

    (Helmholtz Center for Environmental Research)

  • Andreas von Deimling

    (Institute of Pathology, University Hospital of Heidelberg and Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ))

  • Wolfgang Wick

    (Neurology Clinic and National Center for Tumor Diseases University Hospital of Heidelberg
    Clinical Cooperation Unit Neurooncology, German Cancer Research Center (DKFZ))

  • Michael Platten

    (Neurology Clinic and National Center for Tumor Diseases University Hospital of Heidelberg
    Experimental Neuroimmunology Unit, German Cancer Research Center (DKFZ))

Abstract

Activation of the aryl hydrocarbon receptor (AHR) by environmental xenobiotic toxic chemicals, for instance 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin), has been implicated in a variety of cellular processes such as embryogenesis, transformation, tumorigenesis and inflammation. But the identity of an endogenous ligand activating the AHR under physiological conditions in the absence of environmental toxic chemicals is still unknown. Here we identify the tryptophan (Trp) catabolite kynurenine (Kyn) as an endogenous ligand of the human AHR that is constitutively generated by human tumour cells via tryptophan-2,3-dioxygenase (TDO), a liver- and neuron-derived Trp-degrading enzyme not yet implicated in cancer biology. TDO-derived Kyn suppresses antitumour immune responses and promotes tumour-cell survival and motility through the AHR in an autocrine/paracrine fashion. The TDO–AHR pathway is active in human brain tumours and is associated with malignant progression and poor survival. Because Kyn is produced during cancer progression and inflammation in the local microenvironment in amounts sufficient for activating the human AHR, these results provide evidence for a previously unidentified pathophysiological function of the AHR with profound implications for cancer and immune biology.

Suggested Citation

  • Christiane A. Opitz & Ulrike M. Litzenburger & Felix Sahm & Martina Ott & Isabel Tritschler & Saskia Trump & Theresa Schumacher & Leonie Jestaedt & Dieter Schrenk & Michael Weller & Manfred Jugold & G, 2011. "An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor," Nature, Nature, vol. 478(7368), pages 197-203, October.
    • Handle: RePEc:nat:nature:v:478:y:2011:i:7368:d:10.1038_nature10491
    DOI: 10.1038/nature10491
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature10491
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature10491?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

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


    Cited by:

    1. Bo Wang & Jing Chen & Julia S. Caserto & Xi Wang & Minglin Ma, 2022. "An in situ hydrogel-mediated chemo-immunometabolic cancer therapy," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Donghong Zhang & Jinfeng Ning & Tharmarajan Ramprasath & Changjiang Yu & Xiaoxu Zheng & Ping Song & Zhonglin Xie & Ming-Hui Zou, 2022. "Kynurenine promotes neonatal heart regeneration by stimulating cardiomyocyte proliferation and cardiac angiogenesis," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Yun Seok Kim & Bongsub Ko & Da Jung Kim & Jihoon Tak & Chang Yeob Han & Joo-Youn Cho & Won Kim & Sang Geon Kim, 2022. "Induction of the hepatic aryl hydrocarbon receptor by alcohol dysregulates autophagy and phospholipid metabolism via PPP2R2D," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    4. Pravin Kesarwani & Shiva Kant & Yi Zhao & Antony Prabhu & Katie L. Buelow & C. Ryan Miller & Prakash Chinnaiyan, 2023. "Quinolinate promotes macrophage-induced immune tolerance in glioblastoma through the NMDAR/PPARγ signaling axis," 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:nature:v:478:y:2011:i:7368:d:10.1038_nature10491. 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.