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gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis

Bollrath, Julia, Phesse, Toby, von Burstin, Vivian A., Putoczki, Tracy, Bennecke, Moritz, Bateman, Trudie, Nebelsiek, Tim, Lundgren-May, Therese, Canli, Özge, Schwitalla, Sarah, Matthews, Vance, Schmid, Roland M., Kirchner, Thomas, Arkan, Melek C., Ernst, Matthias and Greten, Florian R. 2009. gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis. Cancer Cell 15 (2) , pp. 91-102. 10.1016/j.ccr.2009.01.002

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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 resistance to colitis. Stat3 has the capacity to mediate IL-6- and IL-11-dependent IEC survival and to promote proliferation through G1 and G2/M cell-cycle progression as the common tumor cell-autonomous mechanism that bridges chronic inflammation to tumor promotion.

Item Type: Article
Status: Published
Schools: Biosciences
Subjects: Q Science > QR Microbiology
Publisher: Elsevier
ISSN: 1535-6108
Date of First Compliant Deposit: 20 June 2016
Last Modified: 04 Jun 2017 09:11
URI: http://orca.cf.ac.uk/id/eprint/91569

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