Abstract 4821: Exploring the role of a solid-like condensate in breast and prostate cancer

Abstract

Abstract Cancer cells are exposed to harsh environmental conditions, which they adapt to by engaging various stress response pathways. A common cellular response to these stressors is the assembly of membraneless compartments known as biomolecular condensates. Our lab discovered one such pathway where exposure to environmental stressors reversibly converts nucleoli into solid-like condensates known as Amyloid bodies (A-bodies). A-bodies induce a state of cellular dormancy by sequestering in an amyloid-like state key proteins involved in processes such as DNA replication and cell cycle progression. In vitro experiments showed that suppressing A-body formation in cancer cell lines accelerates tumorigenesis, suggesting that system-wide amyloidogenesis is a mechanism of tumor suppression. The goal of this project was to investigate how A-bodies correlate with tumorigenesis in the context of human tissues. Using formalin-fixed paraffin embedded (FFPE) sections of breast invasive ductal carcinoma and prostate adenocarcinoma, we first confirmed the presence of A-bodies in tumors by staining with the amyloidophilic dye Amylo-glo. In agreement with in vitro data in breast and prostate cancer cell lines, immunohistochemical staining further showed these condensates contain known A-body constituent proteins. Co-staining tissues with Amylo-glo and the proliferation marker Ki67 revealed a negative correlation between A-bodies and cell proliferation, supporting the hypothesis that A-bodies suppress cell growth. Finally, tissue staining comparing primary tumors with distant metastases suggests that A-body biogenesis is reduced in the progression to metastatic disease. Together, our preliminary data presents a biomolecular condensate which can be visualized in human tissues and inversely correlates with cell proliferation. Future directions include examining additional tumor types for the presence of A-bodies and testing the correlation between A-bodies and other markers of proliferation, cell cycle arrest, and environmental stress. Citation Format: Alexander Grunfeld, Michael Bokros, Chloe Kirk, Stephen Lee. Exploring the role of a solid-like condensate in breast and prostate cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4821.