dc.contributor.author | Creagh, Emma | |
dc.contributor.author | Mills, Kingston | |
dc.contributor.author | Flood, Brie | |
dc.contributor.author | Manils, Joan | |
dc.contributor.author | Nulty, Ciara | |
dc.contributor.author | Flis, Ewelina | |
dc.contributor.author | Kenealy, Sinead | |
dc.contributor.author | Barber, Gillian | |
dc.contributor.author | Fay, Joanna | |
dc.contributor.author | Kay, Elaine | |
dc.date.accessioned | 2019-09-24T08:47:04Z | |
dc.date.available | 2019-09-24T08:47:04Z | |
dc.date.issued | 2019 | |
dc.date.submitted | 2019 | en |
dc.identifier.citation | Flood, B., Manils, J., Nulty, C., Flis, E., Kenealy, S., Barber, G., Fay, J., Mills, K.H.G., Kay, E.W., & Creagh, E.M. Caspase-11 regulates the tumour suppressor function of STAT1 in a murine model of colitis-associated carcinogenesis, Oncogene, 38, 14, 2019, 2658-2674 | en |
dc.identifier.issn | 0950-9232 | |
dc.identifier.other | Y | |
dc.identifier.uri | https://www.nature.com/articles/s41388-018-0613-5 | |
dc.identifier.uri | http://hdl.handle.net/2262/89545 | |
dc.description.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 pro-inflammatory 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-1βproduction is more significantly impaired inCasp11−/− 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-11and the non-canonical inflammasome during CAC, and suggest a critical role for caspase-11, linking IL-1
β and STAT1 signalling pathways. | en |
dc.description.sponsorship | This study was supported by Enterprise Ireland (CF-2015–0061P).
B.F. was supported by a Government of Ireland PRTLI PhD programme (scheme #201921, award #12259).
E.F. is an Early Stage Researcher of the EU Horizon 2020 Research and Innovation Programme, TRACT (Marie Sklodowska-
Curie grant agreement No 721906).
S.K. is funded by an SFI Investigator programme grant (12/IP/1400) | en |
dc.format.extent | 2658-2674 | en |
dc.language.iso | en | en |
dc.relation.ispartofseries | Oncogene; | |
dc.relation.ispartofseries | 38; | |
dc.relation.ispartofseries | 14; | |
dc.rights | Y | en |
dc.subject | Molecular Biology | en |
dc.subject | Colon cancer | en |
dc.subject | Inflammation | en |
dc.title | Caspase-11 regulates the tumour suppressor function of STAT1 in a murine model of colitis-associated carcinogenesis | en |
dc.type | Journal Article | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/ecreagh | |
dc.identifier.peoplefinderurl | http://people.tcd.ie/millsk | |
dc.identifier.rssinternalid | 194287 | |
dc.identifier.doi | http://dx.doi.org/10.1038/s41388-018-0613-5 | |
dc.rights.ecaccessrights | openAccess | |
dc.relation.source | https://rdcu.be/bdbYd | en |
dc.subject.TCDTheme | Cancer | en |
dc.subject.TCDTheme | Immunology, Inflammation & Infection | en |
dc.subject.TCDTag | COLORECTAL CANCER | en |
dc.relation.sourceuri | Springer Nature Sharing | en |
dc.identifier.orcid_id | 0000-0001-7631-4370 | |
dc.subject.darat_thematic | Health | en |
dc.status.accessible | N | en |
dc.contributor.sponsor | Enterprise Ireland | en |
dc.contributor.sponsorGrantNumber | CF-2015 0061P | en |
dc.contributor.sponsor | Marie Curie | en |
dc.contributor.sponsorGrantNumber | 721906 | en |
dc.contributor.sponsor | Science Foundation Ireland (SFI) | en |
dc.contributor.sponsorGrantNumber | 12/IP/1400 | en |