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Updated: Jul 14, 2025

An Orthotopic Murine Model of Human Prostate Cancer Metastasis
06:48

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

35.2K

MYC is a regulator of androgen receptor inhibition-induced metabolic requirements in prostate cancer

Preston D Crowell1, Jenna M Giafaglione1, Anthony E Jones2

  • 1Molecular Biology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Cell Reports
|October 10, 2023
PubMed

Insights

Androgen receptor (AR) inhibition in advanced prostate cancer causes metabolic shifts, including mitochondrial elongation and increased oxidative metabolism. Targeting DRP1 and MYC can reverse these changes, offering new therapeutic strategies for treatment resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metabolism

Background:

  • Advanced prostate cancer treatment relies on androgen receptor (AR) signaling pathway inhibitors.
  • Tumor resistance to AR inhibition is a significant clinical challenge.
  • Understanding AR inhibition's impact on tumor cell phenotypes is crucial for overcoming resistance.

Purpose of the Study:

  • To comprehensively characterize the metabolic alterations in prostate cancer cells upon AR blockade.
  • To identify key molecular mediators of AR-blockade-induced metabolic reprogramming.
  • To explore potential therapeutic vulnerabilities arising from these metabolic changes.

Main Methods:

  • Transcriptomics, metabolomics, and bioenergetics analyses were employed.
  • Investigated the role of DRP1 activity and MYC signaling in mediating metabolic phenotypes.
  • Utilized rescue experiments to validate the function of DRP1 and MYC.

Main Results:

  • AR inhibition led to decreased glycolysis, mitochondrial elongation, and enhanced oxidative metabolism.
  • DRP1 activity was identified as a mediator of mitochondrial dynamics.
  • MYC signaling was implicated in regulating glycolytic activity and sensitivity to complex I inhibition.

Conclusions:

  • AR blockade induces significant metabolic reprogramming in prostate cancer cells.
  • DRP1 and MYC are critical regulators of these treatment-induced metabolic phenotypes.
  • Targeting these pathways may offer strategies to overcome resistance to AR-targeted therapies.
Keywords:
CP: CancerCP: Metabolism

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