Author/Authors :
Julia Bollrath، نويسنده , , Julia and Phesse، نويسنده , , Toby J. and von Burstin، نويسنده , , Vivian A. and Putoczki، نويسنده , , Tracy and Bennecke، نويسنده , , Moritz and Bateman، نويسنده , , Trudie and Nebelsiek، نويسنده , , Tim and Lundgren-May، نويسنده , , Therese and Canli، نويسنده , , ضzge and Schwitalla، نويسنده , , Sarah and Matthews، نويسنده , , Vance and Schmid، نويسنده , , Roland M. and Kirchner، نويسنده , , Thomas and Arkan، نويسنده , , Melek C. and Ernst، نويسنده , , Matthias and Greten، نويسنده , , Florian R.، نويسنده ,
Abstract :
Summary
gh 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.
