TY - JOUR
T1 - Inflammation-induced tumorigenesis in the colon is regulated by caspase-1 and NLRC4
AU - Hu, Bo
AU - Elinav, Eran
AU - Huber, Samuel
AU - Booth, Carmen J.
AU - Strowig, Till
AU - Jin, Chengcheng
AU - Eisenbarth, Stephanie C.
AU - Flavell, Richard A.
PY - 2010/12/14
Y1 - 2010/12/14
N2 - 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.
AB - 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.
KW - Colon cancer
KW - Inflammation-induced colorectal cancer
KW - NLR family, pyrin domain containing 3
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U2 - 10.1073/pnas.1016814108
DO - 10.1073/pnas.1016814108
M3 - Article
C2 - 21118981
AN - SCOPUS:78650735879
SN - 0027-8424
VL - 107
SP - 21635
EP - 21640
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 50
ER -
