Related Experiment Video

Updated: Jan 10, 2026

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
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Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis

Published on: June 27, 2020

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Shifted assembly and function of mSWI/SNF family subcomplexes underlie targetable dependencies in dedifferentiated

Jessica D St Laurent1,2,3, Grace D Xu1,2, Alexander W Ying1,2

  • 1Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA 02215.

Biorxiv : the Preprint Server for Biology
|November 24, 2025
PubMed

Insights

Loss of ARID1A/B subunits in endometrial cancer shifts chromatin remodeler complexes, promoting tumor growth. Targeting SMARCA4/2 with inhibitors offers a potential therapeutic strategy, enhancing chemotherapy effectiveness.

Area of Science:

  • Cellular biology
  • Molecular oncology
  • Epigenetics

Background:

  • Mammalian SWI/SNF (mSWI/SNF) complexes are crucial chromatin remodelers regulating gene expression.
  • ARID1A and ARID1B subunits are key for canonical BAF (cBAF) assembly and are often mutated in dedifferentiated/undifferentiated endometrial carcinomas (DDEC/UECs).

Purpose of the Study:

  • To investigate the functional consequences of ARID1A/B loss in DDEC/UECs.
  • To explore the therapeutic potential of targeting mSWI/SNF complexes in these cancers.

Main Methods:

  • Analysis of cellular models and primary human tumor samples.
  • Biochemical assays to assess mSWI/SNF complex abundance and chromatin occupancy.
  • In vivo studies using SMARCA4/2 ATPase inhibitors and carboplatin chemotherapy.

Main Results:

  • ARID1A/B deficiency leads to reduced cBAF and increased Polybromo-associated BAF (PBAF) and non-canonical BAF (ncBAF) complexes.
  • This shift in complex stoichiometry promotes the DDEC oncogenic state.
  • SMARCA4/2 ATPase inhibitors significantly reduced DDEC cell proliferation and tumor growth, synergizing with carboplatin.

Conclusions:

  • Shifted mSWI/SNF complex stoichiometry contributes to oncogenesis in DDEC/UECs.
  • mSWI/SNF small molecule inhibitors represent a promising therapeutic avenue for DDEC/UECs and other cancers with cBAF disruptions.

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