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Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9862-7. doi: 10.1073/pnas.1307575110. Epub 2013 May 21.

Microbiota-induced activation of epithelial IL-6 signaling links inflammasome-driven inflammation with transmissible cancer.

Author information

1
Departments of Immunobiology, Laboratory Medicine, and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.

Erratum in

  • Proc Natl Acad Sci U S A. 2013 Jul 30;110(31):12852. Wunderlich, Claudia [added]; Wunderlich, Thomas [added].

Abstract

The microbiota is pivotal in the pathogenesis of inflammatory bowel disease (IBD)-associated inflammation-induced colorectal cancer (CRC), yet mechanisms for these effects remain poorly characterized. Here, we demonstrate that aberrant inflammasome-induced microbiota plays a critical role in CRC development, where mice deficient in the NOD-like receptor family pyrin domain containing 6 (NLRP6) inflammasome feature enhanced inflammation-induced CRC formation. Intriguingly, WT mice cohoused either with inflammasome-deficient mice or with mice lacking IL-18 feature exacerbated inflammation-induced CRC compared with singly housed WT mice. Enhanced tumorigenesis is dependent on microbiota-induced chemokine (C-C motif) ligand 5 (CCL5)-driven inflammation, which in turn promotes epithelial cell proliferation through local activation of the IL-6 pathway, leading to cancer formation. Altogether, our results mechanistically link the altered microbiota with the pathogenesis of inflammation-induced CRC and suggest that in some conditions, microbiota components may transfer CRC susceptibility between individuals.

KEYWORDS:

ASC; colon cancer; microflora

PMID:
23696660
PMCID:
PMC3683709
DOI:
10.1073/pnas.1307575110
[Indexed for MEDLINE]
Free PMC Article

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