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Updated: Aug 11, 2025

Modeling Colitis-Associated Cancer with Azoxymethane AOM and Dextran Sulfate Sodium DSS
Published on: September 11, 2012
Gasdermin D represses inflammation-induced colon cancer development by regulating apoptosis
Shigekazu Tanaka1, Hajime Orita2,3, Taro Kataoka2
1Mammalian Genetics Laboratory, Genetic Strains Research Center, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540, Japan.
Abstract:
Chronic inflammation is widely recognized as a major risk factor for cancer formation, but the underlying mechanisms are poorly understood. Recently, it was shown that Gasdermin D (GSDMD) protein drives pyroptotic cell death in macrophages on cleavage by inflammatory caspases. Even though the Gsdmd gene is specifically expressed in the intestinal epithelium, the role of Gsdmd in the intestinal tissues remains poorly characterized. In this study, we examined the biological role of Gsdmd in colorectal cancer (CRC) development, employing an azoxymethane/dextran sulfate sodium carcinogenesis model. Results show that GSDMD deficiency enhances CRC development, probably due to decreased apoptosis caused by downregulation of interferon-gamma (IFNγ)-signal transducer and activator 1 (STAT1) signaling. Furthermore, we show that GSDMD protein is diminished in human colorectal cancer, indicating involvement of GSDMD in repression of CRC development in humans. Our findings provide a new insight into functions of Gsdmd/GSDMD in colonic inflammation and human CRC development.
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