Cigarette smoke extract induces malignant transformation and DNA damage via c-MET phosphorylation in human bronchial epithelial cells

被引:0
作者
Wang, Li [1 ,2 ]
Chen, Jin [1 ]
Li, Qianhui [1 ,2 ]
Liu, Anfei [1 ]
Lei, Zhenhan [1 ]
Li, Meixin [1 ]
Yasin, Pazilat [1 ]
Yang, Shuo [1 ]
Ren, Jing [1 ]
Hu, Yijie [1 ]
Ren, Yihui [1 ]
Cheng, Suizhi [1 ,2 ]
Liu, Zhenzhong [1 ]
机构
[1] North Sichuan Med Coll, Sch Publ Hlth, Nanchong 637000, Peoples R China
[2] North Sichuan Med Coll, Sch Pharm, Nanchong 637000, Peoples R China
关键词
Cigarette smoke extract; C-MET; Phosphorylated c-MET; DNA damage; Malignant transformation; HEPATOCYTE GROWTH-FACTOR; CANCER; KINASE; MEDIATOR;
D O I
10.1016/j.ecoenv.2024.116985
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Cigarette smoke, a complex mixture produced by tobacco combustion, contains a variety of carcinogens and can trigger DNA damage. Overactivation of c-MET, a receptor tyrosine kinase, may cause cancer and cellular DNA damage, but the underlying mechanisms are unknown. In this work, we investigated the mechanisms of cigarette smoke extract (CSE) induced malignant transformation and DNA damage in human bronchial epithelial cells (BEAS-2B). The results demonstrated that CSE treatment led to up-regulated mRNA expression of genes associated with the c-MET signaling pathway, increased expression of the DNA damage sensor protein gamma-H2AX, and uncontrolled proliferation in BEAS-2B cells. ATR, ATR, and CHK2, which are involved in DNA damage repair, as well as the phosphorylation of c-MET and a group of kinases (ATM, ATR, CHK1, CHK2) involved in the DNA damage response were all activated by CSE. In addition, CSE activation promotes the phosphorylation modification of ATR, CHK1 proteins associated with DNA damage repair. The addition of PHA665752, a specific inhibitor of c-MET, or knock-down with c-MET both attenuated DNA damage, while overexpression of c-MET exacerbated DNA damage. Thus, c-MET phosphorylation may be involved in CSE-induced DNA damage, providing a potential target for intervention in the prevention and treatment of smoking-induced lung diseases.
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页数:11
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