CXCL14 Promotes Ovarian Cancer Progression and Autophagy Through the IKBKE/NF-κB Pathway

Ovarian cancer remains a leading cause of gynecological malignancy-related deaths, necessitating the identification of novel molecular pathways driving tumor progression. Utilizing a data-driven approach, we conducted bioinformatic analyses of TCGA and GEO datasets, identifying a significant upregulation of CXCL14 in ovarian cancer tissues, which correlates with poor patient survival. Functional assays demonstrated that overexpression of CXCL14 enhances ovarian cancer cell proliferation, invasion, and autophagy. Mechanistically, CXCL14 activates the canonical NF-κB signaling pathway by inducing phosphorylation and degradation of IκBα, leading to phosphorylation and nuclear translocation of p65. Importantly, we identified IKBKE as a critical kinase mediating CXCL14-induced activation of the canonical NF-κB pathway through phosphorylation of IκBα. Knockdown of IKBKE effectively attenuates CXCL14-driven NF-κB activation, thereby suppressing cell proliferation, invasion, and autophagy. In vivo, CXCL14 overexpression markedly enhances ovarian tumor growth, accompanied by increased levels of IKBKE and phosphorylated p65. These findings elucidate a novel regulatory axis, CXCL14/IKBKE/NF-κB, in ovarian cancer progression, highlighting CXCL14 as a potential therapeutic target for ovarian cancer treatment.