| First Author | Flood B | Year | 2019 |
| Journal | Oncogene | Volume | 38 |
| Issue | 14 | Pages | 2658-2674 |
| PubMed ID | 30538296 | Mgi Jnum | J:295056 |
| Mgi Id | MGI:6459597 | Doi | 10.1038/s41388-018-0613-5 |
| Citation | Flood B, et al. (2019) Caspase-11 regulates the tumour suppressor function of STAT1 in a murine model of colitis-associated carcinogenesis. Oncogene 38(14):2658-2674 |
| abstractText | Murine inflammatory caspase-11 has an important role in intestinal epithelial inflammation and barrier function. Activation of the non-canonical inflammasome, mediated by caspase-11, serves as a regulatory pathway for the production of the pro-inflammatory cytokines IL-1beta and IL-18, and has a key role in pyroptotic cell death. We have previously demonstrated a protective role for caspase-11 during dextran sulphate sodium (DSS)-induced colitis, however the importance of caspase-11 during colorectal tumour development remains unclear. Here, we show that Casp11(-/-) mice are highly susceptible to the azoxymethane (AOM)-DSS model of colitis-associated cancer (CAC), compared to their wild type (WT) littermates. We show that deficient IL-18 production occurs at initial inflammation stages of disease, and that IL-1beta production is more significantly impaired in Casp11(-/-) colons during established CAC. We identify defective STAT1 activation in Casp11(-/-) colons during disease progression, and show that IL-1beta signalling induces caspase-11 expression and STAT1 activation in primary murine macrophages and intestinal epithelial cells. These findings uncover an anti-tumour role for the caspase-11 and the non-canonical inflammasome during CAC, and suggest a critical role for caspase-11, linking IL-1beta and STAT1 signalling pathways. |
