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Updated: Jul 11, 2025

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Interactions between BRD4S, LOXL2, and MED1 drive cell cycle transcription in triple-negative breast cancer

Laura Pascual-Reguant1, Queralt Serra-Camprubí2, Debayan Datta1

  • 1Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.

EMBO Molecular Medicine
|November 8, 2023
PubMed

Insights

Simultaneous inhibition of LOXL2 and BRD4 synergistically suppresses triple-negative breast cancer (TNBC) proliferation. Targeting the LOXL2-BRD4 interaction offers a novel therapeutic strategy for TNBC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Triple-negative breast cancer (TNBC) often exhibits resistance to single-agent therapies.
  • Targeted combinatorial approaches are crucial for overcoming treatment resistance in TNBC.

Purpose of the Study:

  • To investigate the synergistic effect of simultaneous LOXL2 and BRD4 inhibition on TNBC proliferation.
  • To elucidate the molecular mechanisms underlying the observed synergistic effect.

Main Methods:

  • In vitro and in vivo studies were conducted to assess TNBC proliferation.
  • Mechanistic studies involved analyzing the interaction of LOXL2 with BRD4S, MED1, and B-MyB.
  • Pharmacological co-inhibition was used to evaluate the impact on transcriptional foci and gene expression.

Main Results:

  • Simultaneous inhibition of LOXL2 and BRD4 synergistically limited TNBC proliferation.
  • LOXL2 was found to interact with BRD4S, MED1, and B-MyB in the nucleus, regulating cell cycle gene transcription.
  • Pharmacological co-inhibition reduced BRD4 nuclear foci and BRD4-MED1 colocalization, suppressing cell cycle gene transcription.

Conclusions:

  • The simultaneous inhibition of LOXL2 and BRD4 presents a promising synergistic strategy for TNBC treatment.
  • Targeting the interaction between BRD4S and LOXL2 could lead to the development of novel therapeutic strategies for TNBC.
Keywords:
cell cyclecombinatorial therapygene expressiontriple-negative breast cancer

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