Laboratory of Innate Immunity and Cell Death Publication

PUBLICATION

The Transcription Factor IRF9 Promotes Colorectal Cancer via Modulating the IL-6/STAT3 Signaling Axis
Author
Sharma B.R.†; Karki R.†; Sundaram B.; Wang Y.; Vogel P.; Kanneganti T.-D.*
Journal
Cancers
Status
2022 Feb
Vol
14(4)
Page
919
Year
2022
File
05_2022_The Transcription Factor IRF9 Promotes Colorectal Cancer via Modulating the IL-6 STAT3 Signaling Axis.pdf (3.7M) 10회 다운로드 DATE : 2023-12-29 15:10:11

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.

Keywords: interferons, IRF9, colitis, colorectal cancer, tumorigenesis, IL-6, STAT3, AOM, DSS, cell death

These authors contributed equally to this work.