Abstract 1680: Roles of EphA2 receptor signaling in prostate cancer development and progression

Abstract Aggressive forms of prostate cancer (PCa), while initially responsive to androgen deprivation therapy (ADT), inevitably become resistant to therapy and are considered castration resistant PCa (CRPC). A major goal of PCa research has been to broadly identify molecular and cellular mechanisms that aid this progression to identify potential therapeutic targets. Using a combination of human data and unique animal models, we found that the receptor tyrosine kinase (RTK) EphA2 is overexpressed specifically in castration resistant and advancing prostate cancers. Furthermore we show that in metastatic PCa the receptor undergoes ligand-independent oncogenic signaling mediated by phosphorylation of EphA2 at S897. Together our data indicate a potential mechanism in PCa progression in which EphA2 becomes overexpressed and aids acquisition of castration resistance via acting as a driver of cell migration, invasion, and proliferation. Citation Format: Ryan Lingerak, Aaron Petty, Hong Guo, Hebei Lin, Xiaojun Shi, Soyeon Kim, Bingcheng Wang. Roles of EphA2 receptor signaling in prostate cancer development and progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1680.