Evidence map›Paper›PMID 34312368›Full record

ArticleCell death & disease2021

C5aR1-positive neutrophils promote breast cancer glycolysis through WTAP-dependent m6A methylation of ENO1.

Baochi Ou, Yuan Liu, Xiaowei Yang, Xiaojun Xu, Yunwen Yan, Jingjie Zhang

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
5.8field-weighted citation impact, top 3% of its field
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

73 citing papers in PubMed, 92 citations in OpenAlex.

  1. Article
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  6. Methylation marks breast cancer metastasis: The roles of mThe Journal of biological chemistry · 2026
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  15. mFrontiers in cell and developmental biology · 2026
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  20. Transcriptional Regulation ofInternational journal of molecular sciences · 2025
    Article

13 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 1 country.

Baochi Ou *Department of Breast Surgery, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, 230022, Hefei, Anhui, China. oubaochi@163.com.ORCID 0000-0001-8147-5232
Yuan LiuDepartment of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, No. 85, Wujin Road, 200080, Shanghai, China.
Xiaowei YangDepartment of Breast Surgery, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, 230022, Hefei, Anhui, China.
Xiaojun XuDepartment of Breast Surgery, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, 230022, Hefei, Anhui, China.
Yunwen YanDepartment of Breast Surgery, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, 230022, Hefei, Anhui, China.
Jingjie Zhang *Department of Breast Surgery, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, 230022, Hefei, Anhui, China.
Anhui Medical University · CNShanghai Jiao Tong University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neutrophils are significant compositions of solid tumors and exert distinct functions in different types of tumors. However, the precise role of neutrophils in the progression of breast cancer (BC) is presently unclear. In this study, by investigating the single-cell RNA sequencing data, we identify a new neutrophil subset, C5aR1-positive neutrophils, that correlates with tumor progression and poor survival for BC patients. Furthermore, it is discovered that C5aR1-positive neutrophils enhance BC cell glycolysis via upregulating ENO1 expression. Mechanically, C5aR1-positive neutrophil-secreted IL1β and TNFα cooperatively activate ERK1/2 signaling, which phosphorylates WTAP at serine341 and thereby stabilizes WTAP protein. The stabilization of WTAP further promotes RNA m6A methylation of ENO1, impacting the glycolytic activity of BC cells. Importantly, C5aR1-positive neutrophils also promote breast cancer growth in vivo, and this effect is abolished by WTAP silencing. In clinical BC samples, increased C5aR1-positive neutrophils correlate with elevated IL1β, TNFα, and ENO1 expression. A high co-expression of C5aR1-positive neutrophil gene signature and ENO1 predicts worse prognosis of BC patients compared with a low co-expression. Collectively, our study reveals a novel subset of C5aR1-positive neutrophils that induces breast cancer glycolysis via increasing ERK1/2-WTAP-dependent m6A methylation of ENO1. These findings support the potential for exploration of C5aR1-positive neutrophils as a therapeutic target in breast cancer.

Indexed as

GlycolysisAdenosineAnimalsBiomarkers, TumorBreast NeoplasmsCell Cycle ProteinsCell Line, TumorDisease ProgressionDNA-Binding ProteinsExtracellular Signal-Regulated MAP KinasesFemaleGene Expression Regulation, NeoplasticHumansMetabolomeMethylationMiceAdenosineBiomarkers, TumorC5AR1 protein, humanCell Cycle ProteinsDNA-Binding ProteinsENO1 protein, humanExtracellular Signal-Regulated MAP KinasesN-methyladenosinePhosphopyruvate HydrataseReceptor, Anaphylatoxin C5aRNA Splicing FactorsTumor Suppressor ProteinsWTAP protein, human

Identifiers

PMID34312368
PMCPMC8313695
OpenAlexW3184509920

What OpenQuestion 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 OpenQuestion graph.