There is growing evidence that the host innate immune system has a critical role 
in regulating carcinogenesis, but the specific receptors involved and the 
importance of their interaction with commensal bacteria need to be elucidated. 
Two major classes of innate immune receptors, the Toll-like receptors and 
Nod-like receptors, many of which are upstream of nuclear factor-kappaB, are 
involved in the detection of intestinal bacteria. The Toll-like receptors have 
been implicated in promoting colon tumorigenesis, but the role of Nod-like 
receptors in regulating tumorigenesis remains unclear. Using an established 
mouse model system of colitis-associated colon tumorigenesis, we show that Nod1 
deficiency results in the increased development of both colitis-associated and 
Apc tumor suppressor-related colon tumors. In the absence of Nod1 signaling, 
there is a greater disruption of the intestinal epithelial cell barrier due to 
chemically induced injury as manifested by increased surface epithelial 
apoptosis early on during chemically induced colitis and increased intestinal 
permeability. The increased intestinal permeability is associated with enhanced 
inflammatory cytokine production and epithelial cell proliferation in 
Nod1-deficient mice as compared with wild-type mice. Depletion of the gut 
microbiota suppressed tumor development in Nod1-deficient mice, thus 
highlighting a link between the commensal bacteria within the intestine and the 
host innate immune Nod1 signaling pathway in the regulation 
inflammation-mediated colon cancer development.