Evidence map›Paper›PMID 40818975›Full record

ArticleNature communications2025

Computational ranking identifies Plexin-B2 in circulating tumor cell clustering with monocytes in breast cancer metastasis.

Emma Schuster, Nurmaa K Dashzeveg, Fangjia Tong, Yuzhi Jia, Lamiaa El-Shennawy, Tong Zhang, Andrew D Hoffman, Reta Birhanu Kitata, Golam Kibria, Youbin Zhang and 22 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. CTC cluster in breast cancer: synergetic metastasis promotion mechanism and transformation path from platelet cloaking to leukocyte escort.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  5. Review
  6. Review
  7. 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

32 authors.

Emma Schuster *Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Nurmaa K Dashzeveg *Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-6702-5187
Fangjia Tong *Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Yuzhi JiaDepartment of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Lamiaa El-ShennawyDepartment of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Tong ZhangBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Andrew D HoffmanDepartment of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Reta Birhanu KitataBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.ORCID http://orcid.org/0000-0002-8973-7679
Golam KibriaDepartment of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Youbin ZhangDivision of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Joshua R SquiresDepartment of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Chunlei ZhengCenter for Artificial Intelligence in Drug Discovery, Case Western Reserve University, Cleveland, OH, USA.
Erika RamosDepartment of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Rokana TaftafDepartment of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
David ScholtenDepartment of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Hannah F AlmubarakDepartment of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0001-5895-9968
Valery Adorno-CruzDepartment of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
David P SullivanDepartment of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-7462-3898
Carolina ReduzziDivision of Hematology and Medical Oncology, Department of Medicine, Weill Cornell School of Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0003-0514-0152
Allegra C MinorDriskill Graduate Program in the Life Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0009-0006-5984-1762
William Purev-OchirDepartment of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Sabina SpahijaDivision of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Rong XuCenter for Artificial Intelligence in Drug Discovery, Case Western Reserve University, Cleveland, OH, USA.ORCID http://orcid.org/0000-0003-3127-4795
Kalliopi P SiziopikouDepartment of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Leonidas C PlataniasDivision of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-9740-7573
Ami ShahDivision of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
William A MullerDepartment of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-4802-2757
William J GradisharDivision of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-2772-3140
Massimo CristofanilliDivision of Hematology and Medical Oncology, Department of Medicine, Weill Cornell School of Medicine, New York, NY, USA.
Chia-Feng TsaiBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Tujin ShiBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA. Tujin.Shi@pnnl.gov.ORCID http://orcid.org/0000-0002-5592-3588
Huiping LiuDepartment of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. huiping.liu@northwestern.edu.ORCID http://orcid.org/0000-0003-4822-7995

Funding

CELLULAR &MOLECULAR BASIS OF DISEASE TRAINING PROGRAMT32GM008061 · NIGMS · NORTHWESTERN UNIVERSITY · PI CARTHEW, RICHARD W. · 1985 to 2022
$17.1M
CARCINOGENESIS TRAINING PROGRAMT32CA009560 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Kathleen Janee Green · 1986 to 2026
$8.4M
TRAINING PROGRAM IN ONCOGENESIS &DEVELOPMENT BIOLOGYT32CA080621 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI EKLUND, ELIZABETH ANN · 2001 to 2018
$4.1M
Clinical analysis and therapeutic development of exosomal ACE2R01AI167272 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Deyu Fang, Huiping Liu · 2022 to 2026
$3.6M
Molecular mechanisms underlying circulating tumor cell aggregationR01CA245699 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LIU, HUIPING · 2020 to 2024
$2.0M
Targeted proteomics technology for accurate quantitative single-cell proteomicsR01GM139858 · NIGMS · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI SHI, TUJIN · 2021 to 2024
$1.6M
Develop a novel therapy with immuno- and onco-targeting dual efficacies to treat the triple negative breast cancerR01CA288387 · NCI · NORTHWESTERN UNIVERSITY · PI Deyu Fang, Huiping Liu · 2025 to 2026
$1.3M
A streamlined platform for phosphoproteome mapping of human tissuesUH3CA256967 · NCI · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI LIU, HUIPING, SHI, TUJIN · 2022 to 2023
$1.2M
Novel functions of PlexinB2 in circulating tumor cell clustersR01CA298232 · NCI · NORTHWESTERN UNIVERSITY · PI Huiping Liu · 2025 to 2026
$1.1M
A streamlined platform for phosphoproteome mapping of human tissuesUG3CA256967 · NCI · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI LIU, HUIPING, SHI, TUJIN · 2020 to 2021
$800k
NCI NIH HHS R01 CA245699NCI NIH HHS R01 CA288387NCI NIH HHS R01 CA298232NCI NIH HHS T32 CA009560NCI NIH HHS T32 CA080621NCI NIH HHS UG3 CA256967NCI NIH HHS UH3 CA256967NIAID NIH HHS R01 AI167272NIGMS NIH HHS R01 GM139858NIGMS NIH HHS T32 GM008061U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA245699
6 · The paper itself

Abstract

Multicellular circulating tumor cell (CTC) clusters can be up to 50 times more efficient than single CTCs in mediating viable metastasis. Here, combining computational ranking and functional determination, we identify the transmembrane protein Plexin-B2 (PLXNB2) as one of the top molecular targets associated with unfavorable distant metastasis-free survival, showing enriched expression in CTC clusters versus single CTCs from patients with advanced breast cancer (mostly female). Loss of PLXNB2 (Plxnb2) reduces the formation of homotypic tumor cell clusters and heterotypic tumor-myeloid cell clusters, reducing spontaneous metastases in female mice bearing human (mouse) breast cancer. Interactions of PLXNB2 with its ligands SEMA4C on tumor cells and SEMA4A on myeloid cells (monocytes) promote homotypic and heterotypic CTC cluster formation, respectively, thereby driving lung metastasis. Global proteomic analysis reveals downstream effectors of the PLXNB2 pathway associated with tumor cell clustering. Thus, PLXNB2 is a therapeutic target for preventing new metastasis in breast cancer.

Indexed as

Breast NeoplasmsLung NeoplasmsMonocytesNeoplastic Cells, CirculatingNerve Tissue ProteinsAnimalsCell Line, TumorFemaleHumansMiceNeoplasm MetastasisProteomicsSemaphorinsNerve Tissue ProteinsPLXNB2 protein, humanPlxnb2 protein, mouseSema4c protein, humanSemaphorins

Identifiers

PMID40818975
PMCPMC12357858

What Socratic holds

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LicenceCC BY
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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.