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http://hdl.handle.net/2445/193139
Title: | Caspase-11 regulates the tumour suppressor function of STAT1 in a murine model of colitis-associated carcinogenesis |
Author: | 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. |
Keywords: | Carcinogènesi Colitis Inflamació Càncer colorectal Carcinogenesis Colitis Inflammation Colorectal cancer |
Issue Date: | 4-Apr-2019 |
Publisher: | Macmillan Publishers |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41388-018-0613-5 |
It is part of: | Oncogene, 2019, vol. 38, num. 14, p. 2658-2674 |
URI: | http://hdl.handle.net/2445/193139 |
Related resource: | https://doi.org/10.1038/s41388-018-0613-5 |
ISSN: | 0950-9232 |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) |
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