Faculty, Staff and Student Publications

Language

English

Publication Date

2-11-2025

Journal

Proceedings of the National Academy of Sciences of the United States of America

DOI

10.1073/pnas.2415308122

PMID

39913208

PMCID

PMC11831193

PubMedCentral® Posted Date

2-6-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Inhibiting the androgen receptor (AR) is effective for treatment of advanced prostate cancers because of their AR-dependent luminal epithelial cell identity. Tumors progress during therapy to castration-resistant prostate cancer (CRPC) by restoring AR signaling and maintaining luminal identity or by converting through lineage plasticity to a neuroendocrine (NE) identity or double-negative CRPC (DNPC) lacking luminal or NE identities. Here, we show that DNPC cells express genes defining basal, club, and hillock epithelial cells from benign prostate. We identified KLF5 as a regulator of genes defining this mixed basal, club, and hillock cell identity in DNPC models. KLF5-mediated upregulation of

Keywords

Male, Humans, Prostatic Neoplasms, Castration-Resistant, Epithelial Cells, Kruppel-Like Transcription Factors, Receptors, Androgen, Transcriptome, Gene Expression Regulation, Neoplastic, Cell Line, Tumor, Receptors, Retinoic Acid, Gene Expression Profiling, Prostate

Comments

This article has been corrected. See Proc Natl Acad Sci U S A. 2025 Mar 28;122(14):e2504762122.

Published Open-Access

yes

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