Inflammation-induced tumorigenesis in the colon is regulated by caspase-1 and NLRC4 |
| |
Authors: | Hu Bo Elinav Eran Huber Samuel Booth Carmen J Strowig Till Jin Chengcheng Eisenbarth Stephanie C Flavell Richard A |
| |
Affiliation: | Department of Immunobiology, Section of Comparative Medicine, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA. |
| |
Abstract: | Chronic inflammation is a known risk factor for tumorigenesis, yet the precise mechanism of this association is currently unknown. The inflammasome, a multiprotein complex formed by NOD-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. Using the 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. |
| |
Keywords: | colon cancer inflammation-induced colorectal cancer NLR family pyrin domain containing 3 |
本文献已被 PubMed 等数据库收录! |
|