Abstract 1482: FKBP52 drives diverse HCC phenotypes through context-dependent targeting of p53

Abstract

Abstract p53 is notably the most frequently mutated protein in hepatocellular carcinoma (HCC), one of the major causes of cancer-related fatalities globally. These mutations often result in some of the most adverse outcomes in HCC, making p53 a prime target for therapeutic intervention. The concept of “hyperstability”of p53 is essential in understanding its gain-of-function and dominant-negative effects in tumorigenesis. However, the mechanisms driving this hyperstability are not completely understood. In this study, we have identified FKBP52, a member of the FK506-binding protein family, as a crucial factor in stabilizing and accumulating p53, irrespective of the type of mutation. Furthermore, our study suggests that FKBP52 could be a valuable biomarker for predicting HCC outcomes. We observed a notable link between FKBP52 levels and the histological differentiation in HCC samples. To corroborate these observations, we performed a series of in vitro and in vivo experiments using liver cancer models. These experiments highlighted the dual nature of FKBP52’s impact on hepatocytes, which varies according to cell type. Given its connection to HCC severity, FKBP52 seems to contribute negatively to the disease’s progression. The insights gained from this study on how FKBP52 influences p53 stabilization are critical. We suggest that targeting the processes upstream of FKBP52 could lead to more effective HCC treatments. These findings emphasize the importance of further investigating this pathway, potentially paving the way for new strategies in liver cancer therapy. Citation Format: Xing Wang, Jingfeng Wu, Chengyan Tang, Xiang Li, Li Zhu, Yaoyu Liu. FKBP52 drives diverse HCC phenotypes through context-dependent targeting of p53 [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 1482.