Related Experiment Video

Updated: Nov 19, 2025

Isolation, Culture, and Characterization of Prostate Cancer-Associated Fibroblasts
09:43

Isolation, Culture, and Characterization of Prostate Cancer-Associated Fibroblasts

Published on: August 1, 2025

455

The androgen receptor/filamin A complex as a target in prostate cancer microenvironment

Marzia Di Donato1, Alice Zamagni2, Giovanni Galasso1

  • 1Department of Precision Medicine, University of Campania 'L. Vanvitelli'- Via L. De Crecchio, 7- 80138, Naples, Italy.

Cell Death & Disease
|January 27, 2021
PubMed

Insights

Prostate cancer fibroblasts migrate and invade when exposed to androgens, driven by a non-functional androgen receptor interacting with filamin A. A peptide disrupting this complex inhibits prostate cancer progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Prostate cancer is a leading cause of cancer death in men, often becoming drug-resistant and metastatic.
  • Current research often focuses on androgen receptor mutations or signaling pathway over-activation in cancer cells.
  • The role of androgen/androgen receptor signaling in cancer-associated fibroblasts (CAFs) and its impact on prostate cancer progression remain unclear.

Purpose of the Study:

  • To investigate the mechanism of androgen/androgen receptor signaling in prostate cancer-associated fibroblasts.
  • To determine the consequences of this signaling on prostate cancer progression and tumor microenvironment.
  • To identify potential therapeutic targets within this pathway.

Main Methods:

  • Analysis of androgen receptor (AR) expression and localization in prostate cancer-associated fibroblasts (CAFs).
  • Investigation of AR co-localization with filamin A (FLNA) upon androgen stimulation.
  • Use of 2D and 3D co-culture models with prostate cancer organoids and CAFs.
  • Assessment of CAF migration, invasiveness, and impact on organoid growth.
  • Application of an AR-derived stapled peptide to disrupt the AR/FLNA complex.
  • Evaluation of extracellular matrix remodeling and protease cascade activation.

Main Results:

  • Prostate cancer-associated fibroblasts express a transcriptionally incompetent AR that co-localizes with FLNA in the extra-nuclear compartment upon androgen challenge.
  • Androgen stimulation enhances CAF migration and invasiveness, leading to increased prostate cancer organoid size.
  • An AR-derived stapled peptide disrupts the AR/FLNA complex, inhibiting androgen-dependent CAF migration and invasiveness.
  • The peptide reduces overall tumor area in 3D co-cultures and impairs the androgen-induced protease cascade involving β1 integrin and MMP1.
  • The AR/FLNA complex is identified as a potential marker, and its disruption a therapeutic strategy.

Conclusions:

  • Androgen signaling through a non-canonical AR/FLNA complex in CAFs promotes prostate cancer progression.
  • Disruption of the AR/FLNA complex using a stapled peptide represents a novel therapeutic strategy.
  • Targeting this pathway in CAFs offers a potential approach to improve prostate cancer treatment, alone or in combination with existing therapies.

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