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Author Notes:

Thirumala-Devi Kanneganti, Department of Immunology, St. Jude Children’s Research Hospital, MS #351, 262 Danny Thomas Place, Memphis Tennessee 38105-3678, USA. Phone: 901.595.3634; Email: Thirumala-devi.kanneganti@stjude.org

RK and TDK conceptualized the study. RK, BRS, and EL designed the methodology. RK, BRS, EL, BB, RKSM, PS, ST, and ARB performed the experiments. RK, BRS, EL, BB, RKSM, PS, ST, HM, ARB, and PV conducted the analysis. RK wrote the original draft; all authors reviewed and edited the draft and approved the final version. TDK acquired the funding and provided resources and supervision.

We thank members of the Kanneganti lab for their comments and suggestions. Several images were acquired at the St. Jude Cell & Tissue Imaging Center, which is supported by St. Jude Children’s Research Hospital and National Cancer Institute grant P30 CA021765-35. We also thank Rebecca Tweedell for scientific editing and writing support. Work from our laboratory is supported by the US NIH (grants AI101935, AI124346, AR056296, and CA163507 to TDK) and the American Lebanese Syrian Associated Charities (to TDK). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

The authors have declared that no conflict of interest exists.



  • Science & Technology
  • Life Sciences & Biomedicine
  • Medicine, Research & Experimental
  • Research & Experimental Medicine

Interferon regulatory factor 1 regulates PANoptosis to prevent colorectal cancer

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Journal Title:



Volume 5, Number 12


Type of Work:

Article | Final Publisher PDF


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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© 2020 American Society for Clinical Investigation

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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