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Updated: Jun 1, 2026

Murine Prostate Micro-dissection and Surgical Castration
08:49

Murine Prostate Micro-dissection and Surgical Castration

Published on: May 11, 2016

Histone methyltransferase KMT2D promotes castration-resistant prostate cancer progression by reactivating AR through

Mayao Luo1,2,3, Chenwei Wu2, Manli Zhou2

  • 1Department of Urology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.

Oncogene
|May 30, 2026
PubMed

Insights

Lysine methyltransferase 2D (KMT2D) drives prostate cancer (PCa) progression by enhancing androgen receptor (AR) signaling and altering metabolism. Inhibiting UTX, crucial for KMT2D, suppresses tumor growth and offers a potential therapeutic strategy for castration-resistant PCa.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Prostate cancer (PCa) progression to castration-resistant PCa (CRPC) involves androgen receptor (AR) reactivation and epigenetic changes.
  • Lysine methyltransferase 2D (KMT2D) is implicated as a potential oncogene in PCa.

Purpose of the Study:

  • To investigate the role of KMT2D in PCa progression and its mechanism of action.
  • To explore the therapeutic potential of targeting KMT2D-related pathways.

Main Methods:

  • Analysis of KMT2D expression in PCa tissues and correlation with prognosis.
  • Investigating KMT2D's interaction with FOXA1 and its effect on AR signaling and chromatin accessibility.
  • Assessing the impact of UTX inhibition on KMT2D function, AR signaling, and tumor proliferation.

Main Results:

  • Elevated KMT2D expression in PCa correlates with poor prognosis.
  • KMT2D recruits FOXA1 to AR enhancers, promoting AR target gene activation and tumor growth.
  • KMT2D-FOXA1-AR axis regulates ketone body metabolism via HMGCS2.
  • UTX inhibition disrupts H3K4me1, suppresses AR signaling, and reduces tumor proliferation.

Conclusions:

  • KMT2D is a critical epigenetic oncogene driving AR-dependent PCa progression.
  • The KMT2D-FOXA1-AR axis is crucial for PCa growth and metabolism.
  • UTX inhibition represents a promising therapeutic strategy for advanced prostate cancer.

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