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

Reactive oxygen species (ROS) could stimulate or inhibit NF-kappa B pathways. However, most results have been obtained on the basis of the exogenous ROS and the molecular target of ROS in NF-kappa B 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-kappa B activation. This study demonstrates that NF-kappa B-inducing kinase (NIK) is a critical target of the endogenous ROS in NF-kappa B pathways. The results indicate that ROS may function as a physiological signalling modulator on NF-kappa B signalling cascades through its ability to facilitate the activity of NIK and subsequent NF-kappa B 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.