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Interferon regulatory factor 1 regulates PANoptosis to prevent colorectal cancer

Rajendra Karki1, Bhesh Raj Sharma1, Ein Lee1,2

  • 1Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

JCI Insight
|June 20, 2020
PubMed

Insights

Interferon regulatory factor 1 (IRF1) protects against colorectal cancer by promoting cell death. IRF1 deficiency impairs pyroptosis, apoptosis, and necroptosis (PANoptosis), increasing susceptibility to colon tumors.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Interferon regulatory factor 1 (IRF1) plays a role in cellular responses and tumorigenesis.
  • Altered IRF1 function is linked to various cancers, but its specific mechanisms in colorectal cancer are unclear.

Purpose of the Study:

  • To investigate the role of IRF1 in regulating colorectal tumorigenesis and tissue homeostasis in vivo.
  • To elucidate the mechanisms by which IRF1 influences cancer development.

Main Methods:

  • Utilized mouse models, including those induced by AOM/DSS and a spontaneous colorectal cancer model.
  • Assessed susceptibility to colorectal tumorigenesis and analyzed cell death pathways in the colon.

Main Results:

  • Mice lacking IRF1 (Irf1-/-) showed increased susceptibility to colorectal tumorigenesis.
  • IRF1 was found to be crucial in both myeloid and epithelial cells for protection.
  • Defective PANoptosis (pyroptosis, apoptosis, and necroptosis) was observed in the colons of Irf1-/- mice, leading to attenuated cell death.

Conclusions:

  • IRF1 acts as an upstream regulator of PANoptosis, inducing essential cell death during colitis-associated tumorigenesis.
  • IRF1 is critical for maintaining colon tissue homeostasis and preventing colorectal cancer development.
Keywords:
CancerColorectal cancerImmunologyInnate immunityOncology

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