CCAR2 negatively regulates IL-8 production in cervical cancer cells

Cell cycle and apoptosis regulator 2 (CCAR2) is a multifaceted protein that controls diverse cellular functions; however, its function in cancer is unclear. To better understand its potential role in cancer, we examined gene expression patterns regulated by CCAR2 in cervical cancer cells. Cytokine and chemokine production by CCAR2-deficient cells increased under oxidative conditions. In particular, H(2)O(2)-treated CCAR2-depleted cells showed a significant increase in interleukin-8 (IL-8) production, indicating a negative regulation of IL-8 by CCAR2. Upregulation of IL-8 expression in CCAR2-deficient cells occurred via activation of transcription factor AP-1. The negative correlation between CCAR2 and IL-8 expression was confirmed by examining mRNA and protein levels in tissues from cervical cancer patients. Furthermore, CCAR2-regulated IL-8 expression is associated with a shorter survival of cervical cancer patients. Overall, the data suggest that CCAR2 plays a critical role in controlling both the cancer secretome and cancer progression.