| First Author | Man SM | Year | 2015 |
| Journal | Cell | Volume | 162 |
| Issue | 1 | Pages | 45-58 |
| PubMed ID | 26095253 | Mgi Jnum | J:224547 |
| Mgi Id | MGI:5688241 | Doi | 10.1016/j.cell.2015.06.001 |
| Citation | Man SM, et al. (2015) Critical Role for the DNA Sensor AIM2 in Stem Cell Proliferation and Cancer. Cell 162(1):45-58 |
| abstractText | Colorectal cancer is a leading cause of cancer-related deaths. Mutations in the innate immune sensor AIM2 are frequently identified in patients with colorectal cancer, but how AIM2 modulates colonic tumorigenesis is unknown. Here, we found that Aim2-deficient mice were hypersusceptible to colonic tumor development. Production of inflammasome-associated cytokines and other inflammatory mediators was largely intact in Aim2-deficient mice; however, intestinal stem cells were prone to uncontrolled proliferation. Aberrant Wnt signaling expanded a population of tumor-initiating stem cells in the absence of AIM2. Susceptibility of Aim2-deficient mice to colorectal tumorigenesis was enhanced by a dysbiotic gut microbiota, which was reduced by reciprocal exchange of gut microbiota with healthy wild-type mice. These findings uncover a synergy between a specific host genetic factor and gut microbiota in determining the susceptibility to colorectal cancer. Therapeutic modulation of AIM2 expression and microbiota has the potential to prevent colorectal cancer. |
