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2019-04-04

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cc by (c) Flood, Brian et al., 2019
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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Recurs relacionat

https://doi.org/10.1038/s41388-018-0613-5

Resum

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.

Matèries

Carcinogènesi, Colitis, Inflamació, Càncer colorectal

Matèries (anglès)

Carcinogenesis, Colitis, Inflammation, Colorectal cancer

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Articles publicats en revistes (Patologia i Terapèutica Experimental)

Citació

FLOOD, Brian, et al. Caspase-11 regulates the tumour suppressor function of STAT1 in a murine model of colitis-associated carcinogenesis. Oncogene. 2019. Vol. 38, num. 14, pags. 2658-2674. ISSN 0950-9232. [consulted: 22 of June of 2026]. Available at: https://hdl.handle.net/2445/193139

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