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

Flood, Brian; Manils, Joan; Nulty, Ciara; Flis, Ewelina; Kenealy, Sinead; Barber, Gillian; Fay, Joanna; Mills, Kingston H. G.; Kay, Elaine W.; Creagh, Emma M.

doi:10.1038/s41388-018-0613-5

Cited by 23 publications

(20 citation statements)

References 61 publications

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“…Survival analysis have revealed that lower NLRP1 are correlated with a shorter patient survival period 69 . In addition, compared to wild-type (WT) littermates, Casp11 −/− mice are highly vulnerable to the AOM/DSS model of CAC 70 . GSDMA was not expressed in normal colorectal epithelial cells but was gradually overexpressed in carcinoma cells, while GSDMD exhibited the opposite trend 71,72 .…”

Section: Role Of Pyroptosis In Tumorigenesis and Metastasismentioning

confidence: 99%

The role of pyroptosis in cancer: pro-cancer or pro-“host”?

et al. 2019

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Programmed cell death (PCD) refers to the way in which cells die depending on specific genes encoding signals or activities. Apoptosis, autophagy, and pyroptosis are all mechanisms of PCD. Among these mechanisms, pyroptosis is mediated by the gasdermin family, accompanied by inflammatory and immune responses. The relationship between pyroptosis and cancer is complex, and the effects of pyroptosis on cancer vary in different tissues and genetic backgrounds. On one hand, pyroptosis can inhibit the occurrence and development of tumors; on the other hand, as a type of proinflammatory death, pyroptosis can form a suitable microenvironment for tumor cell growth and thus promote tumor growth. In addition, the induction of tumor pyroptosis is also considered a potential cancer treatment strategy. Studies have shown that DFNA5 (nonsyndromic hearing impairment protein 5)/GSDME (Gasdermin-E) mRNA methylation results in lower expression levels of DFNA5/GSDME in most tumor cells than in normal cells, making it difficult to activate the pyroptosis in most tumor cells. During the treatment of malignant tumors, appropriate chemotherapeutic drugs can be selected according to the expression levels of DFNA5/GSDME, which can be upregulated in tumor cells, thereby increasing the sensitivity to chemotherapeutic drugs and reducing drug resistance. Therefore, induced pyroptosis may play a predominant role in the treatment of cancer. Here, we review the latest research on the anti-and protumor effects of pyroptosis and its potential applications in cancer treatment. Facts Open questions 1. Does pyroptosis play differential roles in normal and tumor tissues? 2. What are the key signals that initiate pyroptosis? 3. What are the key signaling pathways impacted by pyroptosis in tumors? 4. How can pyroptosis be manipulated to drive tumor fate?

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Section: Role Of Pyroptosis In Tumorigenesis and Metastasismentioning

confidence: 99%

The role of pyroptosis in cancer: pro-cancer or pro-“host”?

et al. 2019

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“…In their study, Flood et al reported heightened susceptibility and exacerbated tumor growth in Casp11 −/− mice compared to their littermate controls. The enhanced tumor burden was associated with reduced levels of both IL-1β and IL-18 which resulted in reduced STAT1 signaling and sub-optimal anti-tumor type I immunity (236). Given that IL-1 cytokines derived from activated inflammasomes evidently play a fundamental role in determining the severity of various gastro-intestinal disorders, consideration must also be given to the composition of the commensal microbiota in these mouse strains.…”

Section: Inflammasomes In Ibdmentioning

confidence: 99%

Divergent Roles for the IL-1 Family in Gastrointestinal Homeostasis and Inflammation

McEntee¹,

Finlay²,

Lavelle³

2019

Front. Immunol.

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Inflammatory disorders of the gastro-intestinal tract are a major cause of morbidity and significant burden from a health and economic perspective in industrialized countries. While the incidence of such conditions has a strong environmental component, in particular dietary composition, epidemiological studies have identified specific hereditary mutations which result in disequilibrium between pro- and anti-inflammatory factors. The IL-1 super-family of cytokines and receptors is highly pleiotropic and plays a fundamental role in the pathogenesis of several auto-inflammatory conditions including rheumatoid arthritis, multiple sclerosis and psoriasis. However, the role of this super-family in the etiology of inflammatory bowel diseases remains incompletely resolved despite extensive research. Herein, we highlight the currently accepted paradigms as they pertain to specific IL-1 family members and focus on some recently described non-classical roles for these pathways in the gastrointestinal tract. Finally, we address some of the shortcomings and sources of variance in the field which to date have yielded several conflicting results from similar studies and discuss the potential effect of these factors on data interpretation.

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“…Accumulating evidence has revealed that inflammasomes are involved in the pathological processes of different tumors [14,30,31], but the specific molecular mechanisms remained incompletely elucidated. In this study, we identified different expression patterns and prognostic characteristics of IRGs among 10 cancers.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Inflammasome‐Related Signature Construction in Kidney Renal Clear Cell Carcinoma Based on a Pan‐Cancer Landscape

Zheng

Wang

Yue

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Objective. To investigate the expression patterns and prognostic characteristics of inflammasome-related genes (IRGs) across cancer types and develop a robust biomarker for the prognosis of KIRC. Methods. The differentially expressed IRGs and prognostic genes among 10 cancers were analyzed based on The Cancer Genome Atlas (TCGA) dataset. Subsequently, an IRGs risk signature was developed in KIRC. Its prognostic accuracy was evaluated by receiver operating characteristic (ROC) analysis. The independent predictive capacity was identified by stratification survival and multivariate Cox analyses. The gene ontology (GO) analysis and principal component analysis (PCA) were performed to explore biological functions of the IRGs signature in KIRC. Results. The expression patterns and prognostic association of IRGs varied from different cancers, while KIRC showed the most abundant survival-related dysregulated IRGs. The IRG signature for KIRC was able to independently predict survival, and the signature genes were mainly involved inimmune-related processes. Conclusions. The pan-cancer analysis provided a comprehensive landscape of IRGs across cancer types and identified a strong association between IRGs and the prognosis of KIRC. Further IRGs signature represented a reliable prognostic predictor for KIRC and verified the prognostic value of inflammasomes in KIRC, contributing to our understanding of therapies targeting inflammasomes for human cancers.

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

Cited by 23 publications

References 61 publications

The role of pyroptosis in cancer: pro-cancer or pro-“host”?

The role of pyroptosis in cancer: pro-cancer or pro-“host”?

Divergent Roles for the IL-1 Family in Gastrointestinal Homeostasis and Inflammation

Prognostic Inflammasome‐Related Signature Construction in Kidney Renal Clear Cell Carcinoma Based on a Pan‐Cancer Landscape

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