Serkan I. Göktuna, Ozge Canli, Julia Bollrath, Alexander André Fingerle, David Horst, Michaela A. Diamanti, Charles Pallangyo, Moritz Bennecke, Tim Nebelsiek, Arun K. Mankan, Roland Lang, David Artis, Yinling Hu, Thomas Patzelt, Jürgen Ruland, Thomas Kirchner, Makoto Mark Taketo, Alain Chariot, Melek C. Arkan, Florian Greten
- The recruitment of immune cells into solid tumors is an essential prerequisite of tumor development. Depending on the prevailing polarization profile of these infiltrating leucocytes, tumorigenesis is either promoted or blocked. Here, we identify IκB kinase α (IKKα) as a central regulator of a tumoricidal microenvironment during intestinal carcinogenesis. Mice deficient in IKKα kinase activity are largely protected from intestinal tumor development that is dependent on the enhanced recruitment of interferon γ (IFNγ)-expressing M1-like myeloid cells. In IKKα mutant mice, M1-like polarization is not controlled in a cell-autonomous manner but, rather, depends on the interplay of both IKKα mutant tumor epithelia and immune cells. Because therapies aiming at the tumor microenvironment rather than directly at the mutated cancer cell may circumvent resistance development, we suggest IKKα as a promising target for colorectal cancer (CRC) therapy.
MetadatenAuthor: | Serkan I. Göktuna, Ozge Canli, Julia Bollrath, Alexander André Fingerle, David Horst, Michaela A. Diamanti, Charles Pallangyo, Moritz Bennecke, Tim Nebelsiek, Arun K. Mankan, Roland Lang, David Artis, Yinling Hu, Thomas Patzelt, Jürgen Ruland, Thomas Kirchner, Makoto Mark Taketo, Alain Chariot, Melek C. Arkan, Florian GretenORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-372455 |
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DOI: | https://doi.org/10.1016/j.celrep.2014.05.006 |
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ISSN: | 2211-1247 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/24882009 |
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Parent Title (English): | Cell reports |
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Publisher: | Cell Press |
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Place of publication: | Maryland Heights, MO |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2015/04/22 |
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Date of first Publication: | 2014/05/29 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2015/04/22 |
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Volume: | 7 |
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Issue: | 6 |
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Page Number: | 12 |
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First Page: | 1914 |
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Last Page: | 1925 |
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Note: | This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). |
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HeBIS-PPN: | 369052099 |
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Institutes: | Medizin / Medizin |
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| Angeschlossene und kooperierende Institutionen / Georg-Speyer-Haus |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung-Nicht kommerziell-Keine Bearbeitung 3.0 |
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