Caspase-11 regulates the tumour suppressor function of STAT1 in a murine model of colitis-associated carcinogenesis

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 rol...

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Autores: 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.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/193139
Acceso en línea:https://hdl.handle.net/2445/193139
Access Level:acceso abierto
Palabra clave:Carcinogènesi
Colitis
Inflamació
Càncer colorectal
Carcinogenesis
Inflammation
Colorectal cancer
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spelling Caspase-11 regulates the tumour suppressor function of STAT1 in a murine model of colitis-associated carcinogenesisFlood, BrianManils Pacheco, JoanNulty, CiaraFlis, EwelinaKenealy, SineadBarber, GillianFay, JoannaH.G. Mills, KingstonKay, Elaine W.Creagh, Emma M.CarcinogènesiColitisInflamacióCàncer colorectalCarcinogenesisColitisInflammationColorectal cancerMurine 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.Macmillan Publishers2023202320192023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion17 p.application/pdfhttps://hdl.handle.net/2445/193139Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1038/s41388-018-0613-5Oncogene, 2019, vol. 38, num. 14, p. 2658-2674https://doi.org/10.1038/s41388-018-0613-5cc by (c) Flood, Brian et al., 2019https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1931392026-05-29T05:05:01Z
dc.title.none.fl_str_mv Caspase-11 regulates the tumour suppressor function of STAT1 in a murine model of colitis-associated carcinogenesis
title Caspase-11 regulates the tumour suppressor function of STAT1 in a murine model of colitis-associated carcinogenesis
spellingShingle Caspase-11 regulates the tumour suppressor function of STAT1 in a murine model of colitis-associated carcinogenesis
Flood, Brian
Carcinogènesi
Colitis
Inflamació
Càncer colorectal
Carcinogenesis
Colitis
Inflammation
Colorectal cancer
title_short Caspase-11 regulates the tumour suppressor function of STAT1 in a murine model of colitis-associated carcinogenesis
title_full Caspase-11 regulates the tumour suppressor function of STAT1 in a murine model of colitis-associated carcinogenesis
title_fullStr Caspase-11 regulates the tumour suppressor function of STAT1 in a murine model of colitis-associated carcinogenesis
title_full_unstemmed Caspase-11 regulates the tumour suppressor function of STAT1 in a murine model of colitis-associated carcinogenesis
title_sort Caspase-11 regulates the tumour suppressor function of STAT1 in a murine model of colitis-associated carcinogenesis
dc.creator.none.fl_str_mv 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.
author Flood, Brian
author_facet 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.
author_role author
author2 Manils Pacheco, Joan
Nulty, Ciara
Flis, Ewelina
Kenealy, Sinead
Barber, Gillian
Fay, Joanna
H.G. Mills, Kingston
Kay, Elaine W.
Creagh, Emma M.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Carcinogènesi
Colitis
Inflamació
Càncer colorectal
Carcinogenesis
Colitis
Inflammation
Colorectal cancer
topic Carcinogènesi
Colitis
Inflamació
Càncer colorectal
Carcinogenesis
Colitis
Inflammation
Colorectal cancer
description 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.
publishDate 2019
dc.date.none.fl_str_mv 2019
2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/193139
url https://hdl.handle.net/2445/193139
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41388-018-0613-5
Oncogene, 2019, vol. 38, num. 14, p. 2658-2674
https://doi.org/10.1038/s41388-018-0613-5
dc.rights.none.fl_str_mv cc by (c) Flood, Brian et al., 2019
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Flood, Brian et al., 2019
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 17 p.
application/pdf
dc.publisher.none.fl_str_mv Macmillan Publishers
publisher.none.fl_str_mv Macmillan Publishers
dc.source.none.fl_str_mv Articles publicats en revistes (Patologia i Terapèutica Experimental)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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