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CHD8 interacts with BCL11A to induce oncogenic transcription in triple negative breast cancer

Mark Waterhouse1,2, Kyren Lazarus1, Maria Francesca Santolla1,3,4

  • 1Department of Pharmacology, University of Cambridge, CB2 1PD, Cambridge, UK.

The EMBO Journal
|May 6, 2025
PubMed

Insights

Researchers identified a specific protein interaction in triple-negative breast cancer (TNBC) involving BCL11A and CHD8. This discovery offers a new strategy for developing targeted TNBC therapies and identified potential drug compounds.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Identifying tumor-specific protein-protein interactions is crucial for targeted cancer therapy development.
  • Triple-negative breast cancer (TNBC) presents unique challenges for therapeutic strategies.
  • The oncogene BCL11A plays significant roles in various cellular processes.

Purpose of the Study:

  • To identify triple-negative breast cancer (TNBC)-specific protein-protein interactions focusing on the oncogene BCL11A.
  • To investigate the role of BCL11A's interaction partners in TNBC pathogenesis.
  • To discover novel therapeutic strategies for TNBC by targeting specific protein interactions.

Main Methods:

  • Proteomic analysis to identify BCL11A protein networks in TNBC and B-cells.
  • Multi-omics analysis to elucidate the functional roles of identified interaction partners.
  • Biophysical assays to confirm direct protein interactions and identify disruptive chemical fragments.

Main Results:

  • The chromatin remodeler CHD8 was identified as a TNBC-specific interaction partner of BCL11A.
  • BCL11A and CHD8 were found to co-regulate targets and synergize in driving TNBC development and progression.
  • Direct BCL11A-CHD8 interaction was confirmed, and chemical fragments disrupting this interaction reduced TNBC cell proliferation.

Conclusions:

  • The study presents a proof-of-principle approach for identifying tumor-specific protein-protein interactions.
  • The BCL11A-CHD8 interaction is a key driver of TNBC pathogenesis.
  • Lead chemical compounds targeting the BCL11A-CHD8 interaction show potential for novel TNBC therapeutics.
Keywords:
BCL11ACHD8TNBCTumour Specific Protein–protein Interactions

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