OCT4 Promotes Ovarian Cancer Cell Metastasis and Angiogenesis via Modulating VEGFR2/LRPPRC Pathway

Background: Due to its high ability of metastasis, ovarian cancer remains the most lethal gynecological malignancy, yet its underlying mechanism remains unconfirmed. Objectives: The main purpose is to probe into the role and regulation mechanism of octamer-binding transcription factor 4 (OCT4) in angiogenesis and metastasis in ovarian cancer.Methods: Immunohistochemistry (IHC) and immunofluorescence in epithelial ovarian cancer specimens and benign ovarian tumor samples were performed, followed by RNA-sequencing and examination of angiogenesis, cell migration and invasion in OCT4 knockdown cell lines and the controls. Co-Immunoprecipitation (Co-IP), mass spectrometry, immunoblotting, immunofluorescence and chromatin immunoprecipitation (ChIP) analyses were conducted along with models of zebrafishes and nude mice of transplanted tumors to gain insights into the specific functions and mechanisms of action of OCT4 in ovarian cancer.Results: Firstly, we discovered that OCT4 expression was enhanced in ovarian cancer tissues significantly, especially in the metastatic lesions, indicating that OCT4 might be a key for the metastasis of ovarian cancer. Furtherly, we observed and verified that OCT4 promoted cell migration and invasion, and induced angiogenesis in vitro and in vivo. Mechanistically, OCT4 modulated the transcription of leucine‑rich PPR motif‑containing protein (LRPPRC)，and furtherly interacted with vascular endothelial growth factor receptor 2 (VEGFR2)/LRPPRC complex and ultimately triggered the downstream FAK/AKT signaling pathway . Conclusions: Together, through models of ovarian cancer cells, zebrafishes and tumor-transplanted mice, this study highlighted the importance of OCT4/LRPPRC/VEGFR2 signaling axis in metastasis of ovarian cancer and angiogenesis. Thus, our finding supplied a potential novel molecular-targeted approach for the treatment of ovarian cancer.