Abstract 4511: The role of Wnt5a signaling pathway in epithelial ovarian cancer progression

Abstract

Abstract Ovarian cancer (OvCa) is the most fatal gynecologic malignancy and the 5th leading cause of cancer death among U.S. women. The majority of women with OvCa (75%) have a very low survival rate (30%), as OvCa is usually diagnosed in late stages after development of intraperitoneal metastasis. Thus, it is indispensable to understand the molecular mechanisms that contribute to OvCa metastatic success, in order to design effective treatment strategies to improve the overall survival of women with OvCa. Wnt5a is a noncanonical Wnt ligand that binds to several cell membrane receptors and activates many downstream signaling pathways that are fundamental for normal developmental processes during embryogenesis. In the past decade, the aberrant activation or inhibition of Wnt5a signaling is emerging as an important event in cancer progression, exerting both oncogenic and tumor-suppressive effects. The role of Wnt5a in OvCa is controversial, as studies report conflicting data. In addition, mechanistic data regarding the contribution of Wnt5a to OvCa progression are largely unavailable. The main aim of this research is to obtain a molecular-level understanding of Wnt5a signaling in OvCa and to investigate its potential roles in influencing OvCa metastatic success. Our data show Wnt5a is prevalent in ascites samples from women in different stages with OvCa, suggesting a role for Wnt5a in promoting disease progression. Data obtained from TCGA (n=583) show high expression of Wnt5a in primary ovarian tumors. Furthermore, Wnt5a enhanced OvCa cells adhesion, migration and invasion in a panel of organotypic and ex vivo functional assays. This was combined with striking morphologic changes characteristic of an invasive phenotype in OvCa cells treated with recombinant Wnt5a protein and formation of tunneling nanotubes (TNT). Overall, our data suggest that Wnt5a plays an oncogenic role in epithelial ovarian cancer cells. More experiments exploring Wnt5a activated pathways and effects in epithelial ovarian cancer cells are under way. Citation Format: Marwa Asem, Allison Young, Carlysa Oyama, Rebecca Burkhalter, Steven Buechler, Daniel Miller, Sharon Stack. The role of Wnt5a signaling pathway in epithelial ovarian cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4511.