Disruption of androgen receptor-cofactor interactions by the RNA-binding protein FUS/TLS alters androgen signalling

G N Brooke1, D A Leach2, R L Culley2

  • 1School of Life Sciences, University of Essex, Wivenhoe Park, Colchester, ESSEX, UK. gbrooke@essex.ac.uk.

Oncogene
|February 6, 2026
PubMed

Insights

FUS protein represses androgen receptor (AR) activity in early prostate cancer, acting as a tumor suppressor. Its expression changes with disease stage, suggesting a complex role in prostate cancer progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Prostate cancer progression is linked to androgen receptor (AR) activity, modulated by cofactors.
  • FUS/TLS is a multifunctional protein with a previously suggested tumor suppressor role in prostate cancer.

Purpose of the Study:

  • To investigate the role of FUS in regulating AR activity in prostate cancer.
  • To understand the expression patterns of FUS in different stages of prostate cancer.

Main Methods:

  • Transcriptomic analysis (RNA-Seq) of LNCaP cells.
  • Reporter assays and domain-specific analyses of FUS.
  • Chromatin immunoprecipitation (ChIP) assays.
  • Quantitative proteomics.

Main Results:

  • FUS significantly overlaps with AR-regulated genes and predominantly represses AR signaling.
  • FUS interacts with AR and cofactors, potentially disrupting transcriptional complex assembly.
  • FUS is down-regulated in primary tumors but up-regulated in advanced, aggressive prostate cancer stages.

Conclusions:

  • FUS acts as a repressor of AR activity and tumor progression in early prostate cancer, explaining its down-regulation.
  • Altered FUS expression in advanced disease may indicate a loss of AR regulatory control, contributing to aggressive tumor behavior.

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