Journal article
gp130-Mediated Stat3 Activation in Enterocytes Regulates Cell Survival and Cell-Cycle Progression during Colitis-Associated Tumorigenesis
J Bollrath, TJ Phesse, VA von Burstin, T Putoczki, M Bennecke, T Bateman, T Nebelsiek, T Lundgren-May, O Canli, S Schwitalla, V Matthews, RM Schmid, T Kirchner, MC Arkan, M Ernst, FR Greten
Cancer Cell | CELL PRESS | Published : 2009
Abstract
Although gastrointestinal cancers are frequently associated with chronic inflammation, the underlying molecular links have not been comprehensively deciphered. Using loss- and gain-of-function mice in a colitis-associated cancer model, we establish here a link comprising the gp130/Stat3 transcription factor signaling axis. Mutagen-induced tumor growth and multiplicity are reduced following intestinal epithelial cell (IEC)-specific Stat3 ablation, while its hyperactivation promotes tumor incidence and growth. Conversely, IEC-specific Stat3 deficiency enhances susceptibility to chemically induced epithelial damage and subsequent mucosal inflammation, while excessive Stat3 activation confers re..
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Awarded by Wilhelm Sander-Stiftung
Funding Acknowledgements
We thank B. Wittig, K. Retzlaff, and V. Feakes for excellent technical assistance. We also thank D. Gumucio for providing villin-Cre mice and W. Reindl for providing Stat3<SUP>lox/lox</SUP> mice with the permission of K. Takeda. M.C.A. was supported by grants obtained from the Wilhelm Sander-Stiftung (2005.146.1) and Deutsche Krebshilfe (107977). M.E. was supported by the National Health and Medical Research Council of Australia (NHMRC) and by an NHMRC Senior Research Fellowship. F.R.G. was supported by the Deutsche Forschungsgemeinschaft (Emmy Noether Programme Gr1916/2-2, SFB 456), Deutsche Krebshilfe (106772), and Fritz Thyssen Stiftung (10.05.2.168).