Deciphering the Transcription Factor Landscape in Prostate Cancer Progression: A Novel Approach to Understand NE Transdifferentiation

Deciphering the Transcription Factor Landscape in Prostate Cancer Progression: A Novel Approach to Understand NE Transdifferentiation

Abstract Prostate cancer (PCa) stands as a leading cause of cancer‐related mortality among men, with treatment‐induced neuroendocrine prostate cancer (NEPC) posing a challenge as an ARPI‐resistant subtype. The role of transcription factors (TFs) in PCa progression and NEPC transdifferentiation remai...

Full description

Saved in:
Bibliographic Details
Main Authors: Yu Wang, Hui Xue, Xiaohui Zhu, Dong Lin, Zheng Chen, Xin Dong, Junru Chen, Mingchen Shi, Yuchao Ni, Jonathan Cao, Rebecca Wu, Connie Kang, Xinyao Pang, Francesco Crea, Yen‐Yi Lin, Colin C. Collins, Martin E. Gleave, Abhijit Parolia, Arul Chinnaiyan, Christopher J. Ong, Yuzhuo Wang
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Advanced Science
Subjects:
adenocarcinoma
De‐differentiation
dormancy
lineage plasticity
NE transdifferentiation
neuroendocrine prostate cancer
Online Access:https://doi.org/10.1002/advs.202404938
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Prostate cancer (PCa) stands as a leading cause of cancer‐related mortality among men, with treatment‐induced neuroendocrine prostate cancer (NEPC) posing a challenge as an ARPI‐resistant subtype. The role of transcription factors (TFs) in PCa progression and NEPC transdifferentiation remains inadequately understood, underscoring a critical gap in current research. In this study, an internal Z score‐based approach is developed to identify lineage‐specific TF profiles in prostatic adenocarcinoma and NEPC for a nuanced understanding of TF expression dynamics. Distinct TF profiles for adenocarcinoma and NEPC are unveiled, identifying 126 shared TFs, 46 adenocarcinoma‐TFs, and 56 NEPC‐TFs, validated across multiple cohorts. Gene Ontology is employed to validate their biological and functional roles in PCa progression. Implications are revealed in cell development, differentiation, and lineage determination. Knockdown experiments suggest that lineage‐TFs are functionally important in maintaining lineage‐specific cell proliferation. Additionally, a longitudinal study on NE transdifferentiation highlights dynamic TF expression shifts, proposing a three‐phases hypothesis for PCa progression mechanisms. This study introduces a groundbreaking approach for deciphering the TF landscape in PCa, providing a molecular basis for adenocarcinoma to NEPC progression, and paving the way for innovative treatment strategies with potential impact on patient outcomes.
ISSN:2198-3844

Similar Items