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Cancer Cell. 2009 Feb 3;15(2):103-13. doi: 10.1016/j.ccr.2009.01.001.

IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer.

Author information

1
Laboratory of Gene Regulation and Signal Transduction, UCSD School of Medicine, University of California San Diego, La Jolla, CA 92093-0723, USA.

Erratum in

  • Cancer Cell. 2009 Mar 3;15(3):241.

Abstract

Colitis-associated cancer (CAC) is the most serious complication of inflammatory bowel disease. Proinflammatory cytokines have been suggested to regulate preneoplastic growth during CAC tumorigenesis. Interleukin 6 (IL-6) is a multifunctional NF-kappaB-regulated cytokine that acts on epithelial and immune cells. Using genetic tools, we now demonstrate that IL-6 is a critical tumor promoter during early CAC tumorigenesis. In addition to enhancing proliferation of tumor-initiating cells, IL-6 produced by lamina propria myeloid cells protects normal and premalignant intestinal epithelial cells (IECs) from apoptosis. The proliferative and survival effects of IL-6 are largely mediated by the transcription factor Stat3, whose IEC-specific ablation has profound impact on CAC tumorigenesis. Thus, the NF-kappaB-IL-6-Stat3 cascade is an important regulator of the proliferation and survival of tumor-initiating IECs.

PMID:
19185845
PMCID:
PMC2667107
DOI:
10.1016/j.ccr.2009.01.001
[Indexed for MEDLINE]
Free PMC Article

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