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Updated: Dec 16, 2025

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
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Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients

Published on: November 19, 2019

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SETD2 Restricts Prostate Cancer Metastasis by Integrating EZH2 and AMPK Signaling Pathways

Huairui Yuan1, Ying Han1, Xuege Wang1

  • 1CAS Key Laboratory of Tissue Microenvironment and Tumor, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.

Cancer Cell
|July 4, 2020
PubMed

Insights

SETD2 delays prostate cancer (PCa) metastasis by methylating EZH2, promoting its degradation. This SETD2-EZH2 pathway integrates metabolic and epigenetic signals to restrict PCa spread.

Area of Science:

  • Epigenetics
  • Cancer Biology
  • Metabolic Signaling

Background:

  • SETD2 and EZH2 catalyze opposing histone marks (H3K36me3 and H3K27me3).
  • The molecular interplay between SETD2 and EZH2 in prostate cancer (PCa) metastasis is not well understood.

Purpose of the Study:

  • To investigate the role of SETD2 in regulating EZH2 activity and its impact on PCa metastasis.
  • To elucidate the mechanism by which SETD2-EZH2 axis influences prostate cancer progression.

Main Methods:

  • Assessed SETD2-mediated methylation of EZH2 in prostate cancer cells.
  • Utilized mouse models with specific SETD2 and EZH2 mutations.
  • Investigated the role of AMPK signaling and FOXO3 in regulating SETD2 expression.

Main Results:

  • SETD2 methylates EZH2, leading to its degradation, thereby delaying PCa metastasis.
  • SETD2 deficiency promotes a metastatic phenotype by inducing Polycomb-repressive chromatin.
  • Mutant EZH2 or SETD2 impaired in EZH2 binding leads to metastatic PCa.
  • Metformin-stimulated AMPK signaling upregulates SETD2 expression via FOXO3.

Conclusions:

  • The SETD2-EZH2 axis acts as a crucial regulator, restricting prostate cancer metastasis.
  • This axis integrates metabolic cues (via AMPK/FOXO3) and epigenetic modifications to control cancer progression.
Keywords:
AMPKEZH2SETD2epigenetic and metabolic dysregulationsmetforminprostate cancer metastasis

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