Evidence map›Paper›PMID 40148973›Full record

ArticleJournal of experimental & clinical cancer research : CR2025

C-FOS promotes the formation of neutrophil extracellular traps and the recruitment of neutrophils in lung metastasis of triple-negative breast cancer.

Shuai Yan, Wenxi Zhao, Juntong Du, Lizhi Teng, Tong Yu, Peng Xu, Jiangnan Liu, Ru Yang, Yuhan Dong, Hongyue Wang and 2 more

Abstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

  1. Review
  2. Neutrophil extracellular traps (NETosis) in gynecologic cancers: from pathogenesis to therapeutic opportunities: a narrative review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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  16. FRA1 (Frontiers in cell and developmental biology · 2025
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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

12 authors.

Shuai YanDepartment of Breast Surgery, The First Afffliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, China.
Wenxi ZhaoDepartment of Breast Surgery, The First Afffliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, China.
Juntong DuDepartment of Breast Surgery, The First Afffliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, China.
Lizhi TengDepartment of Breast Surgery, The First Afffliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, China.
Tong YuDepartment of Breast Surgery, The First Afffliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, China.
Peng XuDepartment of Breast Surgery, The First Afffliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, China.
Jiangnan LiuDepartment of Breast Surgery, The First Afffliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, China.
Ru YangDepartment of Breast Surgery, The First Afffliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, China.
Yuhan DongDepartment of Breast Surgery, The First Afffliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, China.
Hongyue WangDepartment of Breast Surgery, The First Afffliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, China.
Lingran LuDepartment of Breast Surgery, The First Afffliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, China.
Weiyang TaoDepartment of Breast Surgery, The First Afffliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, China. twysci@outlook.com.

Funding

Beijing Medical Award Foundation YXJL‑2021‑0302‑0287First Affiliated Hospital of Harbin Medical University Fund for Distinguished Young Medical Scholars 2021J17Postgraduate Research and Practice Innovation Program of Harbin Medical University YJSCX2023‑63HYD
6 · The paper itself

Abstract

backgroundNeutrophil extracellular traps (NETs) are composed of DNA chains from neutrophils and associated proteolytic enzymes, which play an important role in cancer metastasis. However, the molecular mechanism of NET-mediated lung metastasis in triple-negative breast cancer (TNBC) remains unclear.

methodsThe expression levels of NETs in breast cancer specimens and serum were analyzed and compared with normal samples. Single-cell sequencing bioinformatics analysis was conducted to identify differentially expressed genes and functional enrichment related to NET formation in patients with breast cancer. The effects of c-FOS on neutrophil recruitment and NET formation in TNBC were investigated. The upstream and downstream regulatory mechanisms mediated by c-FOS were explored through in vitro and in vivo experiments. Therapeutic approaches targeting c-FOS for treating TNBC were further studied.

resultsInhibition of c-FOS can suppress tumor growth and lung metastasis in TNBC. Mechanistically, c-FOS promotes transcription by binding to the PAD4 promoter region, facilitating the formation of NETs. Additionally, the activation of the ROS-p38 pathway further enhances c-FOS expression. High expression of c-FOS also promotes the expression of inflammatory factors, facilitating neutrophil recruitment. Both in vitro and in vivo experiments demonstrated that the application of T5224 effectively inhibits the formation of NETs, suppressing lung metastasis and tumor growth.

conclusionIn summary, this study demonstrates that the ROS-p38-cFOS-PAD4 axis can increase NET formation in TNBC and promote the expression of inflammatory factors, facilitating neutrophil recruitment. Therefore, targeting this pathway may help inform new therapeutic strategies and provide new insights for immunotherapy in TNBC.

Indexed as

Extracellular TrapsLung NeoplasmsNeutrophilsProto-Oncogene Proteins c-fosTriple Negative Breast NeoplasmsAnimalsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansMiceNeutrophil InfiltrationFOS protein, humanProto-Oncogene Proteins c-fosc-FOSLung metastasisNeutrophil extracellular trapsNeutrophil recruitmentTriple-negative breast cancer

Identifiers

PMID40148973
PMCPMC11951605

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.