Abstract 573: Cooperative mechanisms driving prostate cancer progression.

Abstract Signal transducer 24 (CD24) is a GPI-anchored cell surface molecule expressed in hematopoietic and immature neuronal cells, but at very low levels in normal differentiated cells. Although commonly used as a stem cell marker, CD24 is also linked to poor prognosis in many cancers, including prostate cancer (PCa). PCa poses major clinical challenges due to its diverse progression mechanisms and pronounced heterogeneity. Recent studies have identified overexpression of Regulator of Chromosome Condensation 2 (RCC2), a multifunctional protein involved in mitosis and cell motility, which contributes to cancer development across tumor types. This study reveals a novel interaction between CD24 and RCC2 in PCa, highlighting their cooperative roles in tumor growth and metastasis. Functionally, RCC2 knockout inhibited proliferation but enhanced migration, while CD24 knockout suppressed both processes; dual knockout synergistically reduced proliferation. In mouse models, RCC2 loss increased lung metastasis, whereas CD24 loss reduced both tumor growth and metastatic spread. Mechanistically, RCC2 regulates motility through vimentin ubiquitination, whereas CD24 promotes RCC2 degradation to modulate β-catenin signaling. Overall, CD24 regulates RCC2 stability and function, influencing key pathways that control proliferation, migration, and epithelial-mesenchymal transition (EMT). This CD24-RCC2-vimentin-β-catenin axis provides new insight into prostate cancer progression and represents a potential therapeutic target to limit metastasis. Citation Format: Runhua Liu, Chao Zhang, Haiyan Yui, Lizhong Wang. Cooperative mechanisms driving prostate cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 573.