The endogenous reactive oxygen species promote NF-kappaB activation by targeting on activation of NF-kappaB-inducing kinase in oral squamous carcinoma cells.
Reactive oxygen species (ROS) could stimulate or inhibit NF-kappaB pathways. However, most results have been obtained on the basis of the exogenous ROS and the molecular target of ROS in NF-kappaB signalling pathways has remained unclear. Here, the oral squamous carcinoma (OSC) cells, with a mild difference in the endogenous ROS level, were used to investigate how slight fluctuation of the endogenous ROS regulates NF-kappaB activation. This study demonstrates that NF-kappaB-inducing kinase (NIK) is a critical target of the endogenous ROS in NF-kappaB pathways. The results indicate that ROS may function as a physiological signalling modulator on NF-kappaB signalling cascades through its ability to facilitate the activity of NIK and subsequent NF-kappaB transactivation. In addition, the data are useful to explain why the altered intracellular microenvironment related to redox state may influence biological behaviours of cancer cells.
Wang
Yumei
Y
Department of Cell Biology, Key Laboratory of the Education Ministry of China for Cell Differentiation and Apoptosis, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Huang
Xinzhi
X
Cang
Hui
H
Gao
Fei
F
Yamamoto
Tetsuya
T
Osaki
Tokio
T
Yi
Jing
J
D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism*; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism*; D000097782:NF-kappaB-Inducing Kinase
D051550:I-kappa B Kinase; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D017382:Reactive Oxygen Species; D000097782:NF-kappaB-Inducing Kinase