|
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
|
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-mwe.cf.ac.uk/id/eprint/91569 |
Citation Data
Cited 634 times in Scopus. View in Scopus. Powered By Scopus® Data
Actions (repository staff only)
 |
Edit Item |
Altmetric
Altmetric
Cardiff University Information Services