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The Transcription Factor IRF9 Promotes Colorectal Cancer via Modulating the IL-6/STAT3 Signaling Axis.
Sharma, Bhesh Raj; Karki, Rajendra; Sundaram, Balamurugan; Wang, Yaqiu; Vogel, Peter; Kanneganti, Thirumala-Devi.
  • Sharma BR; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Karki R; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Sundaram B; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Wang Y; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Vogel P; Animal Resources Center and the Veterinary Pathology Core, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Kanneganti TD; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Cancers (Basel) ; 14(4)2022 Feb 12.
Article in English | MEDLINE | ID: covidwho-1715121
ABSTRACT
Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, and innate immune responses and inflammation are known to affect the course of disease. Interferon (IFN) signaling in particular is critical for modulating inflammation-associated diseases including CRC. While the effects of IFN signaling in CRC have been studied, results have been conflicting. Furthermore, individual molecules in the IFN pathway that could be therapeutically targeted have distinct functions, with many of their diverse roles in CRC remaining unclear. Here, we found that IRF9 had an oncogenic effect in CRC; loss of IRF9 reduced tumorigenesis in both azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced and spontaneous CRC models. IRF9 also reduced DSS-induced colitis and inflammation in the colon, but it had no effect on the NF-κB and MAPK signaling activation. Instead, IRF9 enhanced the transcription and production of the inflammatory cytokine IL-6. By promoting IL-6 release, IRF9 drove the activation of pro-oncogenic STAT3 signaling in the colon. Overall, our study found that IRF9 promoted the development of CRC via modulation of the IL-6/STAT3 signaling axis, identifying multiple potential targets and suggesting new therapeutic strategies for the treatment of CRC.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Year: 2022 Document Type: Article Affiliation country: Cancers14040919

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Year: 2022 Document Type: Article Affiliation country: Cancers14040919