PRDX3 Promotes Lymph Node Metastasis in Cervical Cancer by Activating NF-κB Signaling Pathway and Anoikis Resistance

Lymph node metastasis (LNM) confers significant treatment failure and adverse clinical outcomes in cervical cancer (CCa). However, large unknown lies in the mechanisms underlying LNM in CCa. In this study, we discovered that PRDX3 is elevated in CCa with LNM and associates with poor prognosis in CCa patients. Moreover, multivariate logistic analysis revealed that PRDX3 is an independent predictor of LNM in CCa. Functional investigations demonstrated that PRDX3 promotes invasion, lymphangiogenesis, and LNM of CCa. Mechanistically, PRDX3 activates NF-κB signaling pathway and upregulates the downstream pro-metastatic molecules VEGF-C and MMP-9 in CCa cells. Furthermore, PRDX3 could inhibit the anoikis of detached CCa cells by reducing the ROS level and hence promote LNM in CCa. Importantly, genetic inhibition of PRDX3 potently slows LNM of CCa. These findings highlight a novel PRDX3-mediated mechanism of LNM in CCa and recognize PRDX3 as a promising predictive marker and target of clinical intervention for LNM in CCa.