ArticleCell death & disease2022
Regulation of CCL2 by EZH2 affects tumor-associated macrophages polarization and infiltration in breast cancer.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 81 citations in OpenAlex.
- The role of OLMALINC in small cell lung cancer progression and prognosis.Molecular and cellular biochemistry · 2026Article
- Model-dependent GD2 upregulation in Ewing sarcoma with the EZH2 inhibitor tazemetostat: Prerequisites for combination with GD2-specific CAR T cells.Research square · 2026Article
- Repurposing acetyldigitoxin as a potential EZH2 inhibitor for non-small cell lung cancer: a computational and experimental approach.Journal of computer-aided molecular design · 2026Article
- Genomic and Immune Correlates of EZH2 Expression and Activity in Olfactory Neuroblastoma.Head & neck · 2026Article
- The Research Progress of Tumor-Associated Macrophages in Prostate Cancer.Journal of immunology research · 2026Review
- Mechanoresponsive reprogramming of tumor-associated macrophages during cancer progression.Frontiers in cell and developmental biology · 2026Review
- Pharmacological Inhibition of EZH2 by GSK-343 Attenuates Neuroinflammation in a Mouse Model of Spinal Cord Injury.Journal of neuroscience research · 2026Article
- Review
- Glutamate promotes CCL2 expression to recruit tumor-associated macrophages by restraining EZH2-mediated histone methylation in hepatocellular carcinoma.Oncoimmunology · 2025Article
- Effects of acute exercise on inflammatory and metabolic biomarkers in women: a randomized controlled trial.NPJ breast cancer · 2025Article
- Review
- Single-cell and spatial transcriptomics profile the interaction ofTranslational lung cancer research · 2025Article
- Silibinin Anticancer Effects Through the Modulation of the Tumor Immune Microenvironment in Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Review
- Treating human cancer by targeting EZH2.Genes & diseases · 2025Review
- Myeloid cells: key players in tumor microenvironments.Frontiers of medicine · 2025Review
- Epigenetic regulators combined with tumour immunotherapy: current status and perspectives.Clinical epigenetics · 2025Review
- Unveiling a novel model of cell senescence-related genes for prognostic assessment and immunotherapeutic insights in gastric cancer.Scientific reports · 2025Article
- Review
- Epigenetic Regulation of Stromal and Immune Cells and Therapeutic Targets in the Tumor Microenvironment.Biomolecules · 2025Review
- Chemokine ligand 2: beyond chemotaxis-a multifaceted role in tumor progression.Frontiers in immunology · 2025Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor associated macrophages (TAMs) play an important role in tumorigenesis, development and anti-cancer drug therapy. However, very few epigenetic compounds have been elucidated to affect tumor growth by educating TAMs in the tumor microenvironment (TME). Herein, we identified that EZH2 performs a crucial role in the regulation of TAMs infiltration and protumoral polarization by interacting with human breast cancer (BC) cells. We showed that EZH2 inhibitors-treated BC cells induced M2 macrophage polarization in vitro and in vivo, while EZH2 knockdown exhibited the opposite effect. Mechanistically, inhibition of EZH2 histone methyltransferase alone by EZH2 inhibitors in breast cancer cells could reduce the enrichment of H3K27me3 on CCL2 gene promoter, elevate CCL2 transcription and secretion, contributing to the induction of M2 macrophage polarization and recruitment in TME, which reveal a potential explanation behind the frustrating results of EZH2 inhibitors against breast cancer. On the contrary, EZH2 depletion led to DNA demethylation and subsequent upregulation of miR-124-3p level, which inhibited its target CCL2 expression in the tumor cells, causing arrest of TAMs M2 polarization. Taken together, these data suggested that EZH2 can exert opposite regulatory effects on TAMs polarization through its enzymatic or non-enzymatic activities. Our results also imply that the effect of antitumor drugs on TAMs may affect its therapeutic efficacy, and the combined application with TAMs modifiers should be warranted to achieve great clinical success.
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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.