TRAF4 promotes the malignant progression of high-grade serous ovarian cancer by activating YAP pathway

Abstract

High-grade serous ovarian cancer (HGSOC) accounts for the majority of deaths caused by epithelial ovarian cancer. The specific molecular changes attributable to the pathogenesis of HGSOC are still largely unknown. TRAF4 has been identified to be up-regulated in certain cancers. However, the role and mechanism of TRAF4 in HGSOC remain unclear. In this study, we aim to explore the prognostic value and function of TRAF4 in HGSOC. Immunohistochemical staining and prognostic analysis were used to estimate the prognosis value of TRAF4 in HGSOC. Cell counting assays, colony formation assays, sphere formation assays and tumorigenic assays were used to explore the function of TRAF4 in ovarian cancer cells. Furthermore, RNA-seq, qPCR and western blotting were performed to investigate the molecular mechanism of TRAF4 in ovarian cancer cells. The results showed that TRAF4 was significantly higher expressed in ovarian cancer than normal ovarian epithelium. Moreover, high expression of TRAF4 was significantly associated with shorter overall survival and recurrence-free survival in HGSOC. Knockdown of TRAF4 significantly inhibited the proliferation and tumorigenicity of ovarian cancer cells, whereas overexpression of TRAF4 promoted the proliferation and tumorigenicity of ovarian cancer cells both in vitro and in vivo. Mechanistically, our study demonstrated that TRAF4 expression was positively correlated with the YAP pathway gene signatures, and the malignant progression induced by TRAF4 was inhibited after silencing YAP signaling by its selective inhibitor. In conclusion, our findings suggested that TRAF4 promoted the malignant progression of ovarian cancer cells by activating YAP pathway and might serve as a prognostic biomarker for HGSOC.