gp130-Mediated Stat3 Activation in Enterocytes Regulates Cell Survival and Cell-Cycle Progression during Colitis-Associated Tumorigenesis

Julia Bollrath, Toby J. Phesse, Vivian A. von Burstin, Tracy Putoczki, Moritz Bennecke, Trudie Bateman, Tim Nebelsiek, Therese Lundgren-May, Özge Canli, Sarah Schwitalla, Vance Matthews, Roland M. Schmid, Thomas Kirchner, Melek C. Arkan, Matthias Ernst, Florian R. Greten

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707 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)91-102
Number of pages12
JournalCancer Cell
Issue number2
Publication statusPublished - 3 Feb 2009
Externally publishedYes



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