ArticleCell death & disease2021
C5aR1-positive neutrophils promote breast cancer glycolysis through WTAP-dependent m6A methylation of ENO1.
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.
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Who cites it
73 citing papers in PubMed, 92 citations in OpenAlex.
- HILPDA, Regulated by WTAP in an m6A-Dependent Manner, Enhances Osteosarcoma Development by Inhibiting Ferroptosis and Promoting Glycolysis.Biochemical genetics · 2026Article
- VISTA+ Neutrophils Contribute to Platinum Resistance by Suppressing CD8+ T Cells in High-Grade Serous Ovarian Cancer.Cancer immunology research · 2026Article
- Single-cell and spatial transcriptomics analysis of osteoarthritis: pathway regulation, cell interaction networks, and therapeutic translation.Journal of translational medicine · 2026Review
- ENO1 as an Immunoregulatory Hub in Cancer: Mechanisms and Translational Implications.Biomolecules · 2026Review
- A succinylation-based classifier predicts chemotherapy response in prostate cancer and reveals KAT2A as a therapeutic target.Clinical and translational medicine · 2026Article
- Methylation marks breast cancer metastasis: The roles of mThe Journal of biological chemistry · 2026Review
- Enolase 1: A paradigm of metabolic enzyme moonlighting in tumorigenesis (Review).International journal of oncology · 2026Review
- Tumour cell-intrinsic complement C1r and C1s regulate cancer cell fitness and shape the immune microenvironment in triple-negative breast cancer.Cellular and molecular life sciences : CMLS · 2026Article
- RNA modification-mediated multidimensional crosstalk: a novel perspective on gene expression regulation.Genome biology · 2026Review
- WTAP stabilized by USP7 contributes to enzalutamide resistance in prostate cancer via mediating AKT mCancer gene therapy · 2026Article
- Understanding the role of C5a/C5aR1-mediated complement activation pathway in tumor progression and therapy resistance.Science China. Life sciences · 2026Review
- Article
- The mechanistic role of Wilms tumor 1-associated protein in cancer pathogenesis, immunity, immunotherapy, and therapy resistance.Investigational new drugs · 2026Review
- The role of epigenetic modifications in cancer-associated fibroblasts.Frontiers in medicine · 2026Review
- mFrontiers in cell and developmental biology · 2026Review
- Influence of RNA Modifications on Cancer Metabolism: Interplay with Hypoxia and Therapeutic Implications.Advances in experimental medicine and biology · 2026Review
- RNA Methylation in Cancer Metabolism: from Mechanisms to Therapeutic Opportunities.International journal of biological sciences · 2026Review
- Mitochondria at the intersections of RNA modifications and metabolism reprogramming implications in cell death, tumor microenvironment, and immunotherapy.Journal of hematology & oncology · 2025Review
- Decreased ALKBH5 in neutrophil correlates with disease activity in rheumatoid arthritis and ALKBH5 modulates neutrophil autophagy.Scientific reports · 2025Article
- Transcriptional Regulation ofInternational journal of molecular sciences · 2025Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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