Interferon regulatory factor 1 regulates PANoptosis to prevent colorectal cancer

Interferon regulatory factor 1 (IRF1) regulates diverse biological functions, including modulation of cellular responses involved in tumorigenesis. Genetic mutations and altered IRF1 function are associated with several cancers. Although the function of IRF1 in the immunobiology of cancer is emergin...

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Published in:JCI insight Vol. 5; no. 12
Main Authors: Karki, Rajendra, Sharma, Bhesh Raj, Lee, Ein, Banoth, Balaji, Malireddi, R.K. Subbarao, Samir, Parimal, Tuladhar, Shraddha, Mummareddy, Harisankeerth, Burton, Amanda R., Vogel, Peter, Kanneganti, Thirumala-Devi
Format: Journal Article
Language:English
Published: United States American Society for Clinical Investigation 18.06.2020
Subjects:
Apoptosis
Cancer
Cell death
Colitis
Colorectal cancer
Colorectal carcinoma
Homeostasis
Infections
Inflammasomes
Inflammation
Inflammatory bowel disease
Inflammatory diseases
Interferon
Interferon regulatory factor
Interferon regulatory factor 1
Kinases
Medical prognosis
Mutation
Necroptosis
Proteins
Pyroptosis
Transcription factors
Tumorigenesis
Tumors
Innate immunity
Oncology
Immunology
Colorectal cancer
Cancer
ISSN:2379-3708, 2379-3708
Online Access:Get full text
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Summary:Interferon regulatory factor 1 (IRF1) regulates diverse biological functions, including modulation of cellular responses involved in tumorigenesis. Genetic mutations and altered IRF1 function are associated with several cancers. Although the function of IRF1 in the immunobiology of cancer is emerging, IRF1-specific mechanisms regulating tumorigenesis and tissue homeostasis in vivo are not clear. Here, we found that mice lacking IRF1 were hypersusceptible to colorectal tumorigenesis. IRF1 functions in both the myeloid and epithelial compartments to confer protection against AOM/DSS-induced colorectal tumorigenesis. We further found that IRF1 also prevents tumorigenesis in a spontaneous mouse model of colorectal cancer. The attenuated cell death in the colons of Irf1-/- mice was due to defective pyroptosis, apoptosis, and necroptosis (PANoptosis). IRF1 does not regulate inflammation and the inflammasome in the colon. Overall, our study identified IRF1 as an upstream regulator of PANoptosis to induce cell death during colitis-associated tumorigenesis.
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Authorship note: RK and BRS contributed equally to this work.
ISSN:2379-3708
2379-3708
DOI:10.1172/jci.insight.136720