Inflammation-induced tumorigenesis in the colon is regulated by caspase-1 and NLRC4

Bo Hu, Eran Elinav, Samuel Huber, Carmen J. Booth, Till Strowig, Chengcheng Jin, Stephanie C. Eisenbarth, Richard A. Flavell

Research output: Contribution to journalArticlepeer-review

375 Scopus citations


Chronic inflammation is a known risk factor for tumorigenesis, yet the precise mechanism of this association is currently unknown. The inflammasome, amultiprotein complex formed byNOD-like receptor (NLR) family members, has recently been shown to orchestrate multiple innate and adaptive immune responses, yet its potential role in inflammation-induced cancer has been little studied.Usingthe azoxymethane and dextran sodium sulfate colitis-associated colorectal cancer model, we show that caspase-1-deficient (Casp1-/-) mice have enhanced tumor formation. Surprisingly, the role of caspase- 1 in tumorigenesis was not through regulation of colonic inflammation, but rather through regulation of colonic epithelial cell proliferation and apoptosis. Consequently, caspase-1-deficient mice demonstrate increased colonic epithelial cell proliferation in early stages of injury-induced tumor formation and reduced apoptosis in advanced tumors. We suggest a model in which the NLRC4 inflammasome is central to colonic inflammation-induced tumor formation through regulation of epithelial cell response to injury.

Original languageEnglish (US)
Pages (from-to)21635-21640
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number50
StatePublished - Dec 14 2010
Externally publishedYes


  • Colon cancer
  • Inflammation-induced colorectal cancer
  • NLR family, pyrin domain containing 3

ASJC Scopus subject areas

  • General


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