ArticleCell cycle (Georgetown, Tex.)2018
Tumor-derived lactate induces M2 macrophage polarization via the activation of the ERK/STAT3 signaling pathway in breast cancer.
Article in Cell cycle (Georgetown, Tex.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 309 papers.
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Who cites it
309 citing papers in PubMed, 489 citations in OpenAlex.
- Gut microbiota metabolic reprogramming drives the development of metabolic diseases in the host.Gut microbes · 2026Review
- Lactate as a Signaling Molecule in the Tumor Microenvironment: Implications for Cancer Progression.Biochemical genetics · 2026Review
- A pathomics model for predicting lactate-related prognostic risk groups and their biological mechanisms in lung adenocarcinoma.Translational cancer research · 2026Article
- Metabolic activation using fructose-1,6-bisphosphate microparticles of non-virally LNP-generated CAR-macrophages induces anti-tumor immune responses.Journal of materials chemistry. B · 2026Article
- Tissue-Resident Macrophage in Inflammation and Cancer.MedComm · 2026Review
- Protein Posttranslational Modifications in Immunity: Molecular Mechanisms and Therapeutic Targets.MedComm · 2026Review
- Harnessing macrophage signaling pathways and scalable engineering for next-generation immunotherapies.Signal transduction and targeted therapy · 2026Review
- Emerging Role of Ferroptosis in Chemotherapy-Associated Hepatorenal Toxicity: Mechanistic Insights and Toxicological Perspectives.ACS pharmacology & translational science · 2026Review
- Understanding the epigenetic regulation of lactylation and aberrant lactate metabolism in cancer: From mechanisms to therapeutic strategies (Review).International journal of oncology · 2026Review
- Spatiotemporal multi-omics reveals lineage, spatial and functional heterogeneity of tumor-associated macrophages and therapeutic vulnerabilities in the tumor microenvironment.NPJ precision oncology · 2026Review
- The Tumor-suppressive role of CNTNAP2 in glioma: Dual regulation of the NDN-ERK axis and M2 macrophage polarization.Cancer gene therapy · 2026Article
- The role of lactate in retinal health and disease: mechanisms and potential therapeutic strategies. A narrative review.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Review
- Beyond a waste product: lactate as a master metabolite dictating anti-tumor T-cell fate.Cell death & disease · 2026Review
- Integrin CD11b/CD18 reprograms macrophage polarization by suppressing ERK/STAT3 signaling to enhance antitumor immunity in colitis-associated colorectal cancer.Journal for immunotherapy of cancer · 2026Article
- Metal-based nanoparticles for reprogramming macrophage polarization: Advances in immunomodulatory nanotherapeutics.International journal of pharmaceutics: X · 2026Review
- Oncogenic PIK3CA mutations shape an immunoregulatory microenvironment in mosaic overgrowth disorders.PNAS nexus · 2026Article
- Breast Cancer Milieu Maneuvers Cancer-Associated Macrophages to Synergize Neoplastic Repertoires.Cancers · 2026Review
- Glucose metabolic reprogramming as a driver of immunosuppression in the tumour microenvironment.Clinical and translational medicine · 2026Review
- Research progress and trends on M2 macrophages in breast cancer research: a bibliometric analysis.Discover oncology · 2026Article
- Lactate signaling and immune suppression in tumors: mechanisms and therapeutic implications.Cellular oncology (Dordrecht, Netherlands) · 2026Review
249 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
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Abstract
Tumor-associated macrophages (TAM) are prominent components of tumor microenvironment (TME) and capable of promoting cancer progression. However, the mechanisms for the formation of M2-like TAMs remain enigmatic. Here, we show that lactate is a pivotal oncometabolite in the TME that drives macrophage M2-polarization to promote breast cancer proliferation, migration, and angiogenesis. In addition, we identified that the activation of ERK/STAT3, major signaling molecules in the lactate signaling pathway, deepens our molecular understanding of how lactate educates TAMs. Moreover, suppression of ERK/STAT3 signaling diminished tumor growth and angiogenesis by abolishing lactate-induced M2 macrophage polarization. Finally, research data of the natural compound withanolide D provide evidence for ERK/STAT3 signaling as a potential therapeutic strategy for the prevention and treatment of breast cancer. These findings suggest that the lactate-ERK/STAT3 signaling pathway is a driver of breast cancer progression by stimulating macrophage M2-like polarization and reveal potential new therapeutic targets for breast cancer treatment.
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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.