Evidence map›Paper›PMID 40328966›Full record

ArticleThe EMBO journal2025

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

Mark Waterhouse, Kyren Lazarus, Maria Francesca Santolla, Sara Pensa, Eleanor Williams, Abigail J Q Siu, Hisham Mohammed, Irina Mohorianu, Marcello Maggiolini, Jason Carroll and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The EMBO journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Mark Waterhouse *Department of Pharmacology, University of Cambridge, CB2 1PD, Cambridge, UK.
Kyren Lazarus *Department of Pharmacology, University of Cambridge, CB2 1PD, Cambridge, UK.ORCID http://orcid.org/0000-0003-2691-9560
Maria Francesca Santolla *Department of Pharmacology, University of Cambridge, CB2 1PD, Cambridge, UK.ORCID http://orcid.org/0000-0002-4838-5953
Sara PensaDepartment of Pharmacology, University of Cambridge, CB2 1PD, Cambridge, UK.
Eleanor WilliamsCambridge Stem Cell Institute, University of Cambridge, CB2 0AW, Cambridge, UK.ORCID http://orcid.org/0000-0002-8023-9550
Abigail J Q SiuDepartment of Pharmacology, University of Cambridge, CB2 1PD, Cambridge, UK.ORCID http://orcid.org/0000-0001-7887-1226
Hisham MohammedCancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, 97201, USA.
Irina MohorianuCambridge Stem Cell Institute, University of Cambridge, CB2 0AW, Cambridge, UK.
Marcello MaggioliniDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Rende, Cosenza, Italy.
Jason CarrollCRUK, Cambridge Institute, University of Cambridge, CB2 0AN, Cambridge, UK.ORCID http://orcid.org/0000-0003-3643-0080
Laura S ItzhakiDepartment of Pharmacology, University of Cambridge, CB2 1PD, Cambridge, UK.
Taufiq RahmanDepartment of Pharmacology, University of Cambridge, CB2 1PD, Cambridge, UK.ORCID http://orcid.org/0000-0003-3830-5160
Walid T KhaledDepartment of Pharmacology, University of Cambridge, CB2 1PD, Cambridge, UK. wtk22@cam.ac.uk.ORCID http://orcid.org/0000-0001-9068-5776

Funding

Breast Cancer Now (BCN) 2017MayPR907Cancer Research UK (CRUK) 17348Cancer Research UK (CRUK) 25850Cancer Research UK (CRUK) DCRPGF\100010Fondazione AIRC per la ricerca sul cancro ETS (AIRC) IG n. 21322Ministerio de la Salute, Italy RF-2019-12368937NRRP AnthemNRRP Tech4YouSistema Integrato di Laboratori per l'Ambiente (SILA) PONa3_00341
6 · The paper itself

Abstract

The identification of tumour-specific protein-protein interactions remains a challenge for the development of targeted cancer therapies. In this study we describe our approach for the identification of triple negative breast cancer (TNBC)-specific protein-protein interactions focusing on the oncogene BCL11A. We used a proteomic approach to identify the BCL11A protein networks in TNBC and compared it to its network in B-cells, a cell type in which BCL11A plays crucial roles. This approach identified the chromatin remodeller CHD8 as a TNBC-specific interaction partner of BCL11A. We show that CHD8 also plays a key role in TNBC pathogenesis, with detailed multi-omics analysis revealing that BCL11A and CHD8 co-regulate several targets and synergise to drive tumour development and progression. Using a battery of biophysical assays, we confirm that the BCL11A-CHD8 interaction is direct and identify chemical fragments that disrupt this interaction and affect downstream targets, decreasing proliferation in 3D colony assays. Our study provides a proof-of-principle approach for investigating tumour-specific protein-protein interactions and identifies lead chemical compounds that could be developed into novel therapeutics for TNBC.

Indexed as

DNA-Binding ProteinsGene Expression Regulation, NeoplasticNuclear ProteinsTranscription FactorsTranscription, GeneticTriple Negative Breast NeoplasmsCell Line, TumorCell ProliferationCo-Repressor ProteinsFemaleHumansProtein BindingProteomicsRepressor ProteinsBCL11A protein, humanCHD8 protein, humanCo-Repressor ProteinsDNA-Binding ProteinsNuclear ProteinsRepressor ProteinsTranscription FactorsBCL11ACHD8TNBCTumour Specific Protein–protein Interactions

Identifiers

PMID40328966
PMCPMC12170886

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.