Article (Scientific journals)
IKKalpha promotes intestinal tumorigenesis by limiting recruitment of M1-like polarized myeloid cells.
Göktuna, Serkan; Canli, Ozge; Bollrath, Julia et al.
2014In Cell Reports, 7 (6), p. 1914-25
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Abstract :
[en] 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 IkappaB kinase alpha (IKKalpha) as a central regulator of a tumoricidal microenvironment during intestinal carcinogenesis. Mice deficient in IKKalpha kinase activity are largely protected from intestinal tumor development that is dependent on the enhanced recruitment of interferon gamma (IFNgamma)-expressing M1-like myeloid cells. In IKKalpha mutant mice, M1-like polarization is not controlled in a cell-autonomous manner but, rather, depends on the interplay of both IKKalpha 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 IKKalpha as a promising target for colorectal cancer (CRC) therapy.
Research center :
Giga-Signal Transduction - ULiège
Disciplines :
Oncology
Author, co-author :
Göktuna, Serkan ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Canli, Ozge
Bollrath, Julia
Fingerle, Alexander A.
Horst, David
Diamanti, Michaela A.
Pallangyo, Charles
Bennecke, Moritz
Nebelsiek, Tim
Mankan, Arun K.
Lang, Roland
Artis, David
Hu, Yinling
Patzelt, Thomas
Ruland, Jurgen
Kirchner, Thomas
Taketo, M. Mark
Chariot, Alain ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Arkan, Melek C.
Greten, Florian R.
More authors (10 more) Less
Language :
English
Title :
IKKalpha promotes intestinal tumorigenesis by limiting recruitment of M1-like polarized myeloid cells.
Publication date :
2014
Journal title :
Cell Reports
eISSN :
2211-1247
Publisher :
Elsevier, Amsterdam, Netherlands
Volume :
7
Issue :
6
Pages :
1914-25
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
WELBIO - Walloon Excellence in Life Sciences and Biotechnology [BE]
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Télévie [BE]
Fondation contre le Cancer [BE]
Commentary :
Copyright (c) 2014 The Authors. Published by Elsevier Inc. All rights reserved.
Available on ORBi :
since 03 March 2015

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