Details zur Publikation

Kategorie Textpublikation
Referenztyp Zeitschriften
DOI 10.1038/nature10491
Volltext Shareable Link
Titel (primär) An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor
Autor Opitz, C.A.; Litzenburger, U.M.; Sahm, F.; Ott, M.; Tritschler, I.; Trump, S.; Schumacher, T.; Jestaedt, L.; Schrenk, D.; Weller, M.; Jugold, M.; Guillemin, G.J.; Miller, C.L.; Lutz, C.; Radlwimmer, B.; Lehmann, I.; von Deimling, A.; Wick, W.; Platten, M.
Quelle Nature
Erscheinungsjahr 2011
Department IMMU
Band/Volume 478
Heft 7368
Seite von 197
Seite bis 203
Sprache englisch
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.
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=11625
Opitz, C.A., Litzenburger, U.M., Sahm, F., Ott, M., Tritschler, I., Trump, S., Schumacher, T., Jestaedt, L., Schrenk, D., Weller, M., Jugold, M., Guillemin, G.J., Miller, C.L., Lutz, C., Radlwimmer, B., Lehmann, I., von Deimling, A., Wick, W., Platten, M. (2011):
An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor
Nature 478 (7368), 197 - 203 10.1038/nature10491