Evidence map›Paper›PMID 42321861›Full record

ArticleBreast cancer research : BCR2026

Tumor cell Jagged-1 promotes regional lymphatic metastasis and predicts recurrence in node-positive breast cancer.

Benjamin Gordon, Bhairavi Swaminathan, Seock Won Youn, Natalia Anna Obacz, Rahul Vadakath, Pamela Teneqexhi, Isabel Alvarez-Lopez, Marta Rezola, Sara Manzano, Zuhara Telletxea and 6 more

Abstract read
In one paragraph

Article in Breast cancer research : BCR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

16 authors.

Benjamin GordonDepartment of Physiology and Biophysics, College of Medicine, University of Illinois Chicago, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-3856-0500
Bhairavi SwaminathanDepartment of Physiology and Biophysics, College of Medicine, University of Illinois Chicago, Chicago, IL, USA.
Seock Won YounDepartment of Physiology and Biophysics, College of Medicine, University of Illinois Chicago, Chicago, IL, USA.
Natalia Anna ObaczDepartment of Physiology and Biophysics, College of Medicine, University of Illinois Chicago, Chicago, IL, USA.ORCID http://orcid.org/0009-0000-8804-5497
Rahul VadakathDepartment of Physiology and Biophysics, College of Medicine, University of Illinois Chicago, Chicago, IL, USA.
Pamela TeneqexhiDepartment of Physiology and Biophysics, College of Medicine, University of Illinois Chicago, Chicago, IL, USA.
Isabel Alvarez-LopezBiogipuzkoa (previously known as Biodonostia) Health Research Institute, Donostia-San Sebastian, Spain.
Marta RezolaBiogipuzkoa (previously known as Biodonostia) Health Research Institute, Donostia-San Sebastian, Spain.
Sara ManzanoBiogipuzkoa (previously known as Biodonostia) Health Research Institute, Donostia-San Sebastian, Spain.ORCID http://orcid.org/0000-0002-0052-511X
Zuhara TelletxeaBiogipuzkoa (previously known as Biodonostia) Health Research Institute, Donostia-San Sebastian, Spain.
Ziqiao XuUniversity of Illinois Cancer Center, Chicago, IL, USA.
Zhengjia ChenUniversity of Illinois Cancer Center, Chicago, IL, USA.
Ekrem Emrah ErDepartment of Physiology and Biophysics, College of Medicine, University of Illinois Chicago, Chicago, IL, USA.ORCID http://orcid.org/0000-0001-9456-9684
L A NaicheDepartment of Physiology and Biophysics, College of Medicine, University of Illinois Chicago, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-5031-4804
Maria M CaffarelBiogipuzkoa (previously known as Biodonostia) Health Research Institute, Donostia-San Sebastian, Spain.ORCID http://orcid.org/0000-0002-7442-6827
Jan KitajewskiDepartment of Physiology and Biophysics, College of Medicine, University of Illinois Chicago, Chicago, IL, USA. kitaj@uic.edu.ORCID http://orcid.org/0000-0003-4660-593X

Funding

Notch in Angiogenesis and Vascular BiologyR01HL112626 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI Jan K. Kitajewski · 2012 to 2026
$6.3M
The Study of Jag1-Notch in the Extravasation of Triple Negative Breast Cancer Cells in Metastasis.F30CA257269 · NCI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI GORDON, BENJAMIN · 2021 to 2024
$195k
Congressionally Directed Medical Research Programs W81XWH-18-1-0019NCI NIH HHS 1F30CA257269NCI NIH HHS F30 CA257269NHLBI NIH HHS HL112626-06A1NHLBI NIH HHS R01 HL112626
6 · The paper itself

Abstract

backgroundLymph node metastasis marks a clinically and biologically important transition in breast cancer, reflecting more aggressive disease and increased risk of recurrence. Expression of the Notch ligand JAG1 is linked to poor breast cancer outcomes, but its role in lymphatic dissemination is unclear.

methodsTumor microarray analysis with multiplex staining was performed on synchronous breast and lymph node metastases from node-positive patients to quantify JAG1 expression and correlate findings with clinical outcomes. Orthotopic implantation of human and murine breast cancer cells was used to assess the impact of JAG1 expression on lymphovascular invasion and lymph node metastasis in vivo. The contribution of VEGFR3 signaling to JAG1-mediated lymphatic dissemination was evaluated using a soluble VEGFR3 antagonist. The cell-specific response of lymphatic endothelial cells to JAG1 was assessed by transendothelial migration assays, barrier examination, and sequencing.

resultsMammary tumor cells expressing JAG1 demonstrated increased lymphovascular and lymph node metastasis in mouse models. Inhibition with a soluble VEGFR3 antagonist attenuated JAG1-dependent lymph node metastasis. Exposure to JAG1 disrupted lymphatic endothelial barrier integrity, promoted tumor cell migration across cultured endothelium, and induced pro-inflammatory and pro-adhesion changes in lymphatic endothelial cells. Tumor microarray analyses revealed enrichment of JAG1 in metastatic tumor cells within lymph nodes relative to matched primary tumors. High JAG1 expression in lymph node metastases was significantly associated with increased risk of recurrence.

conclusionsThese findings support a role for tumor cell JAG1 promoting lymphatic dissemination and lymph node metastasis in breast cancer through effects on lymphatic endothelial signaling and barrier function. Enrichment of JAG1 in lymph node metastases and its association with recurrence further support its potential utility as a prognostic biomarker and therapeutic target in node-positive breast cancer.

Indexed as

Breast NeoplasmsJagged-1 ProteinNeoplasm Recurrence, LocalAnimalsCell Line, TumorCell MovementEndothelial CellsFemaleHumansLymphatic MetastasisLymph NodesMicePrognosisSignal TransductionVascular Endothelial Growth Factor Receptor-3JAG1 protein, humanJagged-1 ProteinVascular Endothelial Growth Factor Receptor-3Breast neoplasmsEndothelial barrierJagged1Lymphatic metastasisLymphovascular invasionMetastatic progressionNotch signalingTumor microarrayVEGFR3

Identifiers

PMID42321861
PMCPMC13528135

What Socratic 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 Socratic graph.