ArticleBreast cancer research : BCR2018
Expression of ID4 protein in breast cancer cells induces reprogramming of tumour-associated macrophages.
Article in Breast cancer research : BCR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
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- Investigation of the causal effect and molecular signatures of serum hydroxyvitamin D on atherosclerosis: a Mendelian randomization and transcriptomic approach.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Article
- Combined vitamins D3 and K2 as potential modulators of multiple myeloma cell pathophysiology: transcriptomic and epigenetic effects under standard culture and bone marrow-like conditions.Frontiers in oncology · 2026Article
- The Critical Role of Inhibitor of Differentiation 4 in Breast Cancer: From Mammary Gland Development to Tumor Progression.Cancer medicine · 2025Review
- In vitro model of retinoblastoma derived tumor and stromal cells for tumor microenvironment (TME) studies.Cell death & disease · 2024Article
- scVAG: Unified single-cell clustering via variational-autoencoder integration with Graph Attention Autoencoder.Heliyon · 2024Article
- HIF-1α knockdown suppresses breast cancer metastasis via epithelial mesenchymal transition Abrogation.Heliyon · 2024Article
- ID4-dependent secretion of VEGFA enhances the invasion capability of breast cancer cells and activates YAP/TAZ via integrin β3-VEGFR2 interaction.Cell death & disease · 2024Article
- Inhibitory effect of miR342 on the progression of triple-negative breast cancer cells in vitro and in the mice model.BioImpacts : BI · 2024Article
- Lung Cancer Gene Regulatory Network of Transcription Factors Related to the Hallmarks of Cancer.Current issues in molecular biology · 2023Article
- Identification of a minimum number of genes to predict triple-negative breast cancer subgroups from gene expression profiles.Human genomics · 2022Article
- Re-evaluation of the myoepithelial cells roles in the breast cancer progression.Cancer cell international · 2022Review
- MALAT1-dependent hsa_circ_0076611 regulates translation rate in triple-negative breast cancer.Communications biology · 2022Article
- Single-cell characterization of malignant phenotypes and microenvironment alteration in retinoblastoma.Cell death & disease · 2022Article
- Non-Coding RNAs in the Crosstalk between Breast Cancer Cells and Tumor-Associated Macrophages.Non-coding RNA · 2022Review
- Beyond Immunosuppression: The Multifaceted Functions of Tumor-Promoting Myeloid Cells in Breast Cancers.Frontiers in immunology · 2022Review
- Therapeutic Influence on Important Targets Associated with Chronic Inflammation and Oxidative Stress in Cancer Treatment.Cancers · 2021Review
- Review
- Tumor Microenvironment: Key Players in Triple Negative Breast Cancer Immunomodulation.Cancers · 2021Review
- Tumor-Associated Macrophages as Multifaceted Regulators of Breast Tumor Growth.International journal of molecular sciences · 2021Review
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Authors and funding
15 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAs crucial regulators of the immune response against pathogens, macrophages have been extensively shown also to be important players in several diseases, including cancer. Specifically, breast cancer macrophages tightly control the angiogenic switch and progression to malignancy. ID4, a member of the ID (inhibitors of differentiation) family of proteins, is associated with a stem-like phenotype and poor prognosis in basal-like breast cancer. Moreover, ID4 favours angiogenesis by enhancing the expression of pro-angiogenic cytokines interleukin-8, CXCL1 and vascular endothelial growth factor. In the present study, we investigated whether ID4 protein exerts its pro-angiogenic function while also modulating the activity of tumour-associated macrophages in breast cancer.
methodsWe performed IHC analysis of ID4 protein and macrophage marker CD68 in a triple-negative breast cancer series. Next, we used cell migration assays to evaluate the effect of ID4 expression modulation in breast cancer cells on the motility of co-cultured macrophages. The analysis of breast cancer gene expression data repositories allowed us to evaluate the ability of ID4 to predict survival in subsets of tumours showing high or low macrophage infiltration. By culturing macrophages in conditioned media obtained from breast cancer cells in which ID4 expression was modulated by overexpression or depletion, we identified changes in the expression of ID4-dependent angiogenesis-related transcripts and microRNAs (miRNAs, miRs) in macrophages by RT-qPCR.
resultsWe determined that ID4 and macrophage marker CD68 protein expression were significantly associated in a series of triple-negative breast tumours. Interestingly, ID4 messenger RNA (mRNA) levels robustly predicted survival, specifically in the subset of tumours showing high macrophage infiltration. In vitro and in vivo migration assays demonstrated that expression of ID4 in breast cancer cells stimulates macrophage motility. At the molecular level, ID4 protein expression in breast cancer cells controls, through paracrine signalling, the activation of an angiogenic programme in macrophages. This programme includes both the increase of angiogenesis-related mRNAs and the decrease of members of the anti-angiogenic miR-15b/107 group. Intriguingly, these miRNAs control the expression of the cytokine granulin, whose enhanced expression in macrophages confers increased angiogenic potential.
conclusionsThese results uncover a key role for ID4 in dictating the behaviour of tumour-associated macrophages in breast cancer.
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