The Role of the Noncanonical NF-KappaB Pathway in Colon Cancer
Abstract
Inflammation is an essential mechanism leading to progression of colon cancer. We have found that in mouse models of colonic intestinal inflammation and in inflammatory bowel disease samples that the non-canonical NF-B2 signaling cascade is highly activated in intestinal epithelial cells compared to normal control. Mice disrupted for NIK in intestinal epithelial cells were highly susceptible to several mouse models of colitis as assessed by histology, colon length and body weight loss. These mice demonstrated a significant increase in apoptosis, with a robust regenerative proliferative response compared to wild-type mice. NIK knockout mice also exhibited increased the colonic tumor number and tumor burden following AOM DSS model of colon cancer. Interestingly, mice which overexpress NIK in intestinal epithelial cells were also susceptible to mouse models of inflammation and cancer. Conclusions: Together these data suggest an important rheostatic role of NF-B2 signaling in intestine. Future work is focusing on the precise mechanism by which NF-kB2signaling can modulate intestinal inflammation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2016
- Accession Number
- AD1019351
Entities
People
- Yatrik M. Shah
Organizations
- University of Michigan