The endogenous reactive oxygen species promote NF-kappaB activation by targeting on activation of NF-kappaB-inducing kinase in oral squamous carcinoma cells

• Published in: Free radical research Vol. 41; no. 9; pp. 963 - 971
• Main Authors: Wang, Yumei, Huang, Xinzhi, Cang, Hui, Gao, Fei, Yamamoto, Tetsuya, Osaki, Tokio, Yi, Jing
• Format: Journal Article
• Language: English
• Published: England 01.09.2007
• Subjects: Carcinoma, Squamous Cell - metabolism; Cell Line, Tumor; Humans; I-kappa B Kinase - metabolism; Mouth Neoplasms - metabolism; Mutation; NF-kappa B - metabolism; NF-kappaB-Inducing Kinase; Phosphorylation; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Reactive Oxygen Species - analysis; Reactive Oxygen Species - metabolism
• ISSN: 1071-5762; 1029-2470

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.