Epigenetic Derepression of PROX1 Promotes Neuroendocrine Prostate Cancer Progression.

ABSTRACT: Histologic transformation of prostate cancer from adenocarcinoma to neuroendocrine prostate cancer (NEPC) is associated with aggressive disease and poor prognosis. This lineage transition is accompanied by polycomb complex 2-mediated epigenetic derepression of cell fate-determining transcription factors, including prospero homeobox 1 (PROX1). In this study, we sought to functionally characterize the role of PROX1 in NEPC. An unbiased CRISPR screen in two NEPC patient-derived organoid models demonstrated high cellular dependency for PROX1. Knockout of PROX1 impeded tumor growth in NEPC models, and overexpression of PROX1 promoted tumor growth and spontaneous metastasis in prostate adenocarcinoma. Transcriptomic and cistromic analyses across castration-resistant adenocarcinoma and neuroendoc

SUBMITTER: Venkadakrishnan VB 

PROVIDER: S-EPMC12492970 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature