gp130-Mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis (Cancer Cell, 2009, 15:91-102)

報告日期: 2009/04/17
報告時間: 17:10/18:00
報告學生: 陳怡成(英文報告)
講評老師: 賴明德

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


Julia Bollrath,1,4 Toby J. Phesse,2,4 Vivian A. von Burstin,1 Tracy Putoczki,2 Moritz Bennecke,1 Trudie Bateman,2,5Tim Nebelsiek,1 Therese Lundgren-May,2 O¨ zge Canli,1 Sarah Schwitalla,1 Vance Matthews,2,6 Roland M. Schmid,1Thomas Kirchner,3 Melek C. Arkan,1 Matthias Ernst,2,* and Florian R. Greten1,*

Cancer Cell, 15, 91–102, February 3, 2009


Speaker: 陳怡成

Commentator: 賴明德 老師

Date: 2009/04/17

Time: 17:10-18:00

Room: 602


A causal link between inflammation and cancer is well accepted. Gastrointestinal cancers are frequently associated with chronic inflammation, but the underlying molecular links have not been comprehensively deciphered, and several recent studies in genetically modified mice have helped to dissect and characterize some of the underlying molecular events. In this paper, we used loss- and gain-of-function mice in a colitis-associated cancer model to establish here a link comprising the gp130/Stat3 transcription factor signaling axis. epithelial depletion of Stat3 blocks early tumor development and that the extent of Stat3 activation modifies canonical Wnt signaling-initiated tumorigenesis. Stat3 protects enterocytes from apoptosis during early tumor promotionin AOM+ DSS-challenged Stat3-deficiend mice in intestinal epithelial cell, we could observe fail to induction of Bcl-XL, survivin, and Hsp70 protein expression, rather than differential regulation of Bcl-2, Mcl-1, Bak, and Bax, and then increased the rate of apoptosis. Stat3 stimulates regeneration and proliferation during colitis and intestinal epithelial cell-autonomous mechanism by which stat3-dependent hyperproliferation mediates the protective effect against DSS-induced colitis. Hyperproliferation of stat3 in gp130Y757F mice is associated with cell-cycle alterations during G1 and G2/M phase. The stat3-associated antiapoptotic, prosurvival effects not only are present within preneoplastic cells during early tumor promotion in the CAC model but remain important for tumor epithelia.