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Super-enhancer-hijacking RBBP7 potentiates metastasis and stemness of breast cancer via recruiting NuRD complex subunit LSD1

  • 0Department of Thyroid and Breast Surgery, Southwest Hospital, Army Medical University, Chongqing, China.
Journal of Translational Medicine +

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March 4, 2025

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March 4, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

RBBP7 promotes breast cancer stemness and metastasis by interacting with LSD1. Targeting the SE-RBBP7-LSD1 axis with ORY-1001 offers a potential therapeutic strategy for breast cancer.

Area Of Science

  • Oncology
  • Epigenetics
  • Molecular Biology

Background

  • Aberrant epigenetic and transcriptional events drive cancer progression.
  • RBBP7's role in breast cancer (BCa) stemness and metastasis requires investigation.

Purpose Of The Study

  • To uncover the epigenetic roles of RBBP7 in breast cancer stemness and metastasis.
  • To identify RBBP7 as a potential therapeutic target for breast cancer.

Main Methods

  • Bioinformatic analysis, CCK8, colony formation, and Transwell assays assessed RBBP7's clinical significance and oncogenic functions.
  • ChIP-qPCR, dual-luciferase reporter, tumor sphere formation, and tail vein injection assays investigated epigenetic mechanisms and metastatic efficiency.
  • Patient-derived organoid (PDO) and patient-derived xenograft (PDX) models evaluated ORY-1001 efficacy.

Main Results

  • RBBP7 is upregulated in BCa, correlating with poor prognosis and enhanced proliferation/metastasis.
  • A novel RBBP7-super-enhancer (SE) was identified, crucial for maintaining RBBP7 levels and BCa malignancy.
  • RBBP7 promotes stemness by recruiting LSD1 to demethylate H3K9me3 at stemness gene promoters (SOX9/SOX2/OCT4/CCND1), enhancing self-renewal and metastasis.

Conclusions

  • The SE-RBBP7-LSD1 axis is a key driver of breast cancer stemness and metastasis.
  • Pharmacological inhibition of LSD1 by ORY-1001 effectively suppressed RBBP7-high BCa growth and stemness.
  • The SE-RBBP7-LSD1 axis represents a promising therapeutic target for breast cancer treatment.

Keywords:

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