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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/193139
Caspase-11 regulates the tumour suppressor function of STAT1 in a murine model of colitis-associated carcinogenesis
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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 proinflammatory cytokines IL-1β 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-1β 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-1β 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-1β and STAT1 signalling pathways.
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FLOOD, Brian, MANILS PACHECO, Joan, NULTY, Ciara, FLIS, Ewelina, KENEALY, Sinead, BARBER, Gillian, FAY, Joanna, H.G. MILLS, Kingston, KAY, Elaine w., CREAGH, Emma m.. Caspase-11 regulates the tumour suppressor function of STAT1 in a murine model of colitis-associated carcinogenesis. _Oncogene_. 2019. Vol. 38, núm. 14, pàgs. 2658-2674. [consulta: 20 de gener de 2026]. ISSN: 0950-9232. [Disponible a: https://hdl.handle.net/2445/193139]