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The Innate Immune Receptor Nod1 Protects the Intestine from Inflammation-Induced Tumorigenesis
Open accessAbstract
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.
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“It was reported that Nod1–/– mice have increased levels of intestinal permeability and inflammation in the murine DSS-induced colitis model compared with wild type mice,174 suggesting an important role in intestinal barrier function.”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [174]
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Metadata
- Authors
- Chen, G. Y., Shaw, M. H., Redondo, G., & Núñez, G.
- Affiliations
- University of Michigan (US)
- 2Pathology,
- Venue
- Cancer Research
- Published
- 2008-12-15
- Volume
- 68
- Issue
- 24
- Pages
- 10060-10067
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC2804847
- OpenAlex
- W1990955264
- Cited by
- 261
- References
- 45
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 6 · 2023: 15 · 2022: 18 · 2021: 33 · 2020: 15 · 2019: 18 · 2018: 19 · 2017: 15 · 2016: 12 · 2015: 11 · 2014: 19 · 2013: 22 · 2012: 18
- FWCI
- 3.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Michigan
- National Institutes of Health
- National Heart, Lung, and Blood Institute (T32HL007517)
- National Cancer Institute (K08CA133185, T32CA009357)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK 61707, R01DK061707)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- NOD1, NOD-like receptors, innate immunity, colitis-associated colorectal cancer, APC tumor suppressor, intestinal epithelial barrier, intestinal permeability, epithelial apoptosis, inflammatory cytokines, gut microbiota, commensal bacteria, chemically induced colitis, carcinogenesis
- MeSH terms
- Animals, Azoxymethane, Colitis, Colonic Neoplasms, Female, Immunity, Innate, Intestines, Male, Mice, Inbred C57BL, Receptors, Immunologic, RNA, Messenger, Specific Pathogen-Free Organisms, Cytokines, Dextran Sulfate, Genes, APC, Chemokines, Mice, Nod1 Signaling Adaptor Protein
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