CKAP4 Promotes Ovarian Cancer By Activating Mutant P53

Objective: To explore the interaction between CKAP4 and mutant p53 in high-grade serous ovarian cancer and its underlying mechanism during the ovarian cancer development.Method: We used Sanger box and GEPIA to analyze the expression levels of CKAP4 in normal tissues and tumor tissues in TCGA and GEO databases,and analyzed the survival prognosis of patients by KM-plotter.Then the interaction between CKAP4 and mutant p53 was verified by Co-IP;and we overexpressed or knocked down CKAP4 in human ovarian cancer cell lines followed by RT-q PCR to detect the expression of mtp53 target genes,Ch IP assay to detect the transcription activity of NF-Y target genes and detected by CCK-8 and transwell assays.The ovarian cancer cell lines stably overexpressing and knocking down CKAP4 were used to perform subcutaneous tumorigenesis experiments in nude mice to verify the in vivo effect of CKAP4.Afterwards,CKAP4 was overexpressed in p53-null or knocked-down ovarian cancer cell lines to verify whether CKAP4 affects the malignant phenotype of ovarian cancer cells in a p53-dependent manner.Results: The expression of CKAP4 was increased in ovarian cancer,and ovarian cancer patients with high expression of CKAP4 had poor prognosis.Co-IP results demonstrated that CKAP4 binds to mutant p53,but not wild-type p53.Overexpression of CKAP4 can up-regulate mutant p53 target genes,up-regulate the transcription activity of NF-Y target genes and CKAP4 is correlated with the expression of CDK1,CDC25 C,NFKB2 and other genes.Overexpression of CKAP4 can promote the proliferation,migration and subcutaneous tumorigenicity in nude mice of ovarian cancer cells.Conversely,knockdown of CKAP4 suppressed these malignant properties.Overexpression of CKAP4 in cell lines lacking mutant p53 failed to promote proliferation and migration of ovarian cancer cells.Conclusion: The expression of CKAP4 protein in ovarian tumors is higher than that in the relative normal tissues and is associated with poor prognosis,CKAP4 promotes the malignant properties of ovarian cancer cells such as proliferation and invasion via the Mtp53-NF-Y axis.