TRAF4 promotes endometrial cancer cell growth and migration by activation of PI3K/AKT/Oct4 signaling.

Endometrial cancer (EC) is ranked as the most common gynecologic malignancy of the female genital tract and the fourth most common neoplasia in women. Accumulated evidences reveal that TRAF4 plays a critical role in the progress of various cancers, but its functions in EC remains unclear. This study aimed to explore the role and mechanism of TRAF4 in EC progress. TRAF4 expression in EC tissues were assessed by qRT-PCR, IHC and western blot. TRAF4 expression in Ishikawa and primary EC cells was inhibited and overexpressed by transient transfections. Thereafter, cell proliferation was identified by combination of clone formation assay and Ki67 staining assay. Cell viability, apoptosis and migration were respectively measured by MTT assay, flow cytometry assay and transwell migration assay. Furthermore, qRT-PCR and western blot analysis were mainly performed to assess the expression levels of apoptosis-related proteins and PI3K/AKT/Oct4 pathway proteins. TRAF4 was up-regulated in EC tissues. Knockdown of TRAF4 induced cell apoptosis and inhibited cell proliferation and migration. However, TRAF4 overexpression increased cell proliferation and migration. Furthermore, we found TRAF4 down-regulation repressed the activation of PI3K/AKT signaling pathway in Ishikawa and primary EC cells. We also found that Oct4 was a downstream factor of PI3K/AKT pathway and was positively regulated by TRAF4. TRAF4 might increase cell viability through PI3K/AKT/Oct4 pathway. The present study demonstrated that TRAF4 might exert an oncogenic role in EC progress via its regulation of PI3K/AKT/Oct4 pathway.