The Olive Phenolic <i>S</i>-(-)-Hydroxyoleocanthal Attenuates Neuroendocrine Prostate Cancer via Modulation of EPHA3-Centered Oncogenic Network.

ABSTRACT: Background/Objectives. Prostate cancer (PCa) is the second leading cause of cancer-related mortality among men in the United States. Treatment with second-generation androgen receptor (AR) inhibitors, such as enzalutamide, can trigger lineage plasticity, promoting the transdifferentiation of PCa cells into an AR-independent, poorly differentiated neuroendocrine phenotype (NEPC). The receptor tyrosine kinase EPHA3 is a critical driver for NEPC. It is overexpressed in PCa, particularly in androgen-independent and neuroendocrine subtypes. EPHA3 activates c-Myc signaling to enhance EZH2 expression, promoting histone H3K27 trimethylation. The neural transcription factor BRN2 functions upstream of both EZH2 and ASCL1. The latter regulates the Notch pathway ligand DLL3, thereby orchestrati

SUBMITTER: Tarun MTI 

PROVIDER: S-EPMC12785029 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature