ROS-generating oxidase NOX1 promotes the self-renewal activity of CD133+ thyroid cancer cells through activation of the Akt signaling.

Thyroid cancer results from unregulated expansion of a self-renewing tumor-initiating cell population. The regulatory pathways essential for sustaining the self-renewal of tumor-initiating cells remain largely unknown. Reactive oxygen species (ROS) play a vital role in tumor initiation and progression. In the present study, we found that the level of ROS was higher in CD133 + thyroid cancer cells than in CD133- thyroid cancer cells. The transcriptional level of ROS-generating oxidase NADPH oxidase 1 (NOX1) is high in CD133 + thyroid cancer cells. Activation of STAT3 through phosphorylation is responsible for high activation of NOX1 transcription in CD133 + thyroid cancer cells. Knock down of NOX1 obviously reduced the level of ROS and inhibited the self-renewal activity and tumorigenicity of CD133 + thyroid cancer cells. Furthermore, knock down of NOX1 reduced the activity of PI3K/Akt pathway. Overexpression of active form of Akt rescued the negative effect of NOX1 knockdown on the self-renewal capability of CD133 + thyroid cancer cells. Together, NOX1 promotes the self-renewal property of CD133 + thyroid cancer cells at least partly through activation of the Akt signaling.