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Publication : Gasdermin D represses inflammation-induced colon cancer development by regulating apoptosis.

First Author  Tanaka S Year  2023
Journal  Carcinogenesis Volume  44
Issue  4 Pages  341-349
PubMed ID  36753047 Mgi Jnum  J:337009
Mgi Id  MGI:7493578 Doi  10.1093/carcin/bgad005
Citation  Tanaka S, et al. (2023) Gasdermin D represses inflammation-induced colon cancer development by regulating apoptosis. Carcinogenesis 44(4):341-349
abstractText  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 (IFNgamma)-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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