Silencing DEK downregulates cervical cancer tumorigenesis and metastasis via the DEK/p-Ser9-GSK-3β/p-Tyr216-GSK-3β/β-catenin axis

Cervical cancer is the second most common gynecological malignancy. The mechanisms of the genesis and progression of cervical cancer are complicated and not thoroughly understood. DEK is reported as an oncogene in various cancers, such as acute myeloid leukemia, bladder cancer, breast cancer and hepatocellular cancer. However, its role in cervical cancer has not been well studied. In our study, we confirmed the DEK protein as an oncoprotein in cervical cancer tissues which is correlated to cervical cancer FIGO staging and tumor type. Moreover, in vitro loss of DEK inhibited cervical cancer cell proliferation, migration and invasion. We proved that silencing DEK downregulated Wnt/beta-catenin and MMP-9, and silencing DEK increased GSK-3 beta activity via regulating its phosphorylation instead of translation. Silencing DEK reduced p-Ser9-GSK-3 beta and increased p-Tyr216-GSK-beta, which resulted in beta-catenin degradation. Finally, the xenograft model in nude mice proved that silencing DEK impaired cervical cancer cell tumorigenicity. This research unveiled the function of DEK in tumorigenesis and metastasis via the DEK/p-Ser9GSK-3 beta/p-Tyr216-GSK-3 beta/beta-catenin axis in cervical cancer and gave insights into DEK-targeting therapy for patients suffering from cervical cancer.