Evidence map›Paper›PMID 38762624›Full record

ArticleCommunications biology2024

Brain endothelial cells promote breast cancer cell extravasation to the brain via EGFR-DOCK4-RAC1 signalling.

Chiara Galloni, Teklu Egnuni, Safoura Zahed Mohajerani, Jiaqi Ye, Sibylle Mittnacht, Valerie Speirs, Mihaela Lorger, Georgia Mavria

Abstract read
In one paragraph

Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
–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

14 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  5. Article
  6. CSDE1 Drives Glycolysis and the Progression of Prostate Cancer Through RAC1-Dependent RAS/MAPK Activation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
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  8. Review
  9. Review
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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

8 authors.

Chiara GalloniLeeds Institute of Medical Research, University of Leeds, Leeds, UK.
Teklu EgnuniLeeds Institute of Medical Research, University of Leeds, Leeds, UK.
Safoura Zahed MohajeraniLeeds Institute of Medical Research, University of Leeds, Leeds, UK.ORCID 0000-0002-1591-7589
Jiaqi YeLeeds Institute of Medical Research, University of Leeds, Leeds, UK.
Sibylle MittnachtUCL Cancer Institute, University College London, London, UK.ORCID 0000-0002-0463-6554
Valerie SpeirsInstitute of Medical Sciences, University of Aberdeen, Aberdeen, UK.ORCID 0000-0002-0602-4666
Mihaela LorgerLeeds Institute of Medical Research, University of Leeds, Leeds, UK.ORCID 0000-0002-2943-2152
Georgia MavriaLeeds Institute of Medical Research, University of Leeds, Leeds, UK. G.Mavria@leeds.ac.uk.ORCID 0000-0002-7227-1614

Funding

Breast Cancer Now (BCN) PR748
6 · The paper itself

Abstract

The role of endothelial cells in promoting cancer cell extravasation to the brain during the interaction of cancer cells with the vasculature is not well characterised. We show that brain endothelial cells activate EGFR signalling in triple-negative breast cancer cells with propensity to metastasise to the brain. This activation is dependent on soluble factors secreted by brain endothelial cells, and occurs via the RAC1 GEF DOCK4, which is required for breast cancer cell extravasation to the brain in vivo. Knockdown of DOCK4 inhibits breast cancer cell entrance to the brain without affecting cancer cell survival or growth. Defective extravasation is associated with loss of elongated morphology preceding intercalation into brain endothelium. We also show that brain endothelial cells promote paracrine stimulation of mesenchymal-like morphology of breast cancer cells via DOCK4, DOCK9, RAC1 and CDC42. This stimulation is accompanied by EGFR activation necessary for brain metastatic breast cancer cell elongation which can be reversed by the EGFR inhibitor Afatinib. Our findings suggest that brain endothelial cells promote metastasis through activation of cell signalling that renders breast cancer cells competent for extravasation. This represents a paradigm of brain endothelial cells influencing the signalling and metastatic competency of breast cancer cells.

Indexed as

BrainBrain NeoplasmsEndothelial CellsErbB Receptorsrac1 GTP-Binding ProteinSignal TransductionAnimalsBreast NeoplasmsCell Line, TumorFemaleGTPase-Activating ProteinsHumansMiceTriple Negative Breast NeoplasmsEGFR protein, humanErbB ReceptorsGTPase-Activating Proteinsrac1 GTP-Binding ProteinRAC1 protein, human

Identifiers

PMID38762624
PMCPMC11102446

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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.