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

Autor:	Tanaka S; Mammalian Genetics Laboratory, Genetic Strains Research Center, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540, Japan., Orita H; Shizuoka Medical Research Center for Disaster, Juntendo University, Shizuoka Hospital, 1129 Nagaoka, Izunokuni, Shizuoka 410-2295, Japan.; Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo Bunkyo Ward, Tokyo 113-8421, Japan., Kataoka T; Shizuoka Medical Research Center for Disaster, Juntendo University, Shizuoka Hospital, 1129 Nagaoka, Izunokuni, Shizuoka 410-2295, Japan., Miyazaki M; Shizuoka Medical Research Center for Disaster, Juntendo University, Shizuoka Hospital, 1129 Nagaoka, Izunokuni, Shizuoka 410-2295, Japan., Saeki H; Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo Bunkyo Ward, Tokyo 113-8421, Japan., Wada R; Department of Pathology, Juntendo University Shizuoka Hospital, 1129 Nagaoka, Izunokuni, Shizuoka 410-2295, Japan., Brock MV; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Fukunaga T; Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo Bunkyo Ward, Tokyo 113-8421, Japan., Amano T; Mammalian Genetics Laboratory, Genetic Strains Research Center, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540, Japan.; Next Generation Human Disease Model Team, RIKEN BioResource Research Center, Tsukuba 305-0074, Japan., Shiroishi T; Mammalian Genetics Laboratory, Genetic Strains Research Center, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540, Japan.; RIKEN BioResource Research Center, Tsukuba 305-0074, Japan.
Jazyk:	angličtina
Zdroj:	Carcinogenesis [Carcinogenesis] 2023 Jun 24; Vol. 44 (4), pp. 341-349.
DOI:	10.1093/carcin/bgad005
Abstrakt:	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. (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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