ArticleCell communication and signaling : CCS2018
Nrf2 activation drive macrophages polarization and cancer cell epithelial-mesenchymal transition during interaction.
Article in Cell communication and signaling : CCS, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 3 of them syntheses that pooled it.
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Who cites it
134 citing papers in PubMed, 3 syntheses or guidelines pooled it, 183 citations in OpenAlex.
- Mechanisms of obesity- and diabetes mellitus-related pancreatic carcinogenesis: a comprehensive and systematic review.Signal transduction and targeted therapy · 2023Pooled it
- Cutting edges and therapeutic opportunities on tumor-associated macrophages in lung cancer.Frontiers in immunology · 2022Pooled it
- Dual roles and therapeutic potential of Keap1-Nrf2 pathway in pancreatic cancer: a systematic review.Cell communication and signaling : CCS · 2019Pooled it
- Research advances on tumor-associated macrophages in pancreatic cancer.Biochemistry and biophysics reports · 2026Review
- Lactate and lactylation in hepatocellular carcinoma: A new frontier in metabolic-epigenetic interactions.Medical oncology (Northwood, London, England) · 2026Review
- Obesity-derived metabolites modulate anti-tumor immunity in the tumor microenvironment: from mechanisms to clinical applications.BMC medicine · 2026Review
- The role of NRF2 in human cancers: Pre-clinical insights paving the way for clinical trials.Journal of pharmaceutical analysis · 2026Review
- Tumor-associated macrophages promote ferroptosis resistance in glioblastoma by stimulating iron-loaded extracellular vesicle release.Journal of neuro-oncology · 2026Article
- Extracellular vesicles from canine mammary tumor cells promote macrophage M2 polarization and enhance tumor progression.Veterinary research communications · 2026Article
- Targeted inhibition of Nrf2 potentiates antitumor immunity and enhances the efficacy of immunotherapy in hepatocellular carcinoma.Journal for immunotherapy of cancer · 2026Article
- Papillary renal cell carcinoma with high-ABCC2 shows an immune-evasive profile associated with favorable response to immunotherapy.The Journal of pathology · 2026Article
- Exploring the mechanism and therapeutic potential of BUB1 in regulating esophageal cancer progression based on 5-FU target prediction.Discover oncology · 2026Article
- Triptolide inhibits ovarian cancer growth and metastasis via reprogramming of tumor-associated macrophages.Cell stress · 2026Article
- MYC at the tumor-immune interface: mechanisms of immune escape and immunotherapy resistance.Frontiers in immunology · 2026Review
- The role of macrophages in radiation-induced lung injury: from pathological mechanisms to therapeutic targets.Frontiers in immunology · 2026Review
- From metabolism to genome integrity: NRF2 as a key mediator of cancer therapy response.Frontiers in cell and developmental biology · 2026Review
- The NRF2 signaling pathway in hepatocellular carcinoma: dual roles, epigenetic reprogramming, and therapeutic opportunities in metabolic vulnerability.Frontiers in oncology · 2026Review
- Glabridin attenuates LTA‑induced alveolar macrophage migration via activation of the Nrf2/HO‑1 pathway.Molecular medicine reports · 2026Article
- MYC as a key target for melanoma therapy.Frontiers in cell and developmental biology · 2026Review
- The landscape of gut microbiota in hepatocarcinogenesis: a comprehensive review of pathogenesis and therapeutic interventions.International journal of surgery (London, England) · 2026Review
74 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
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Abstract
backgroundThe M2 phenotype of tumor-associated macrophages (TAM) inhibits the anti-tumor inflammation, increases angiogenesis and promotes tumor progression. The transcription factor Nuclear Factor (erythroid-derived 2)-Like 2 (Nrf2) not only modulates the angiogenesis but also plays the anti-inflammatory role through inhibiting pro-inflammatory cytokines expression; however, the role of Nrf2 in the cancer cell and macrophages interaction is not clear.
methodsHepatocellular carcinoma cells (Hep G2 and Huh 7) and pancreatic cancer cells (SUIT2 and Panc-1) were co-cultured with monocytes cells (THP-1) or peripheral blood monocytes derived macrophages, then the phenotype changes of macrophages and epithelial-mesenchymal transition of cancer cells were detected. Also, the role of Nrf2 in cancer cells and macrophages interaction were investigated.
resultsIn this study, we found that cancer cells could induce an M2-like macrophage characterized by up-regulation of CD163 and Arg1, and down-regulation of IL-1b and IL-6 through Nrf2 activation. Also, Nrf2 activation of macrophages promoted VEGF expression. The Nrf2 activation of macrophages correlated with the reactive oxygen species induced by cancer cells derived lactate. Cancer cells educated macrophages could activate Nrf2 of the cancer cells, in turn, to increase cancer cells epithelial-mesenchymal transition (EMT) through paracrine VEGF. These findings suggested that Nrf2 played the important role in the cancer cells and macrophages interaction.
conclusionsMacrophage Nrf2 activation by cancer cell-derived lactate skews macrophages polarization towards an M2-like phenotype and educated macrophages activate Nrf2 of the cancer cells to promote EMT of cancer cells. This study provides a new understanding of the role of Nrf2 in the cancer cell and TAM interaction and suggests a potential therapeutic target.
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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.