ArticleThoracic cancer2023
Lactate secreted by esophageal cancer cells induces M2 macrophage polarization via the AKT/ERK pathway.
Article in Thoracic cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
- Review
- Suppression of Tumor Aggression Through Metabolic Reprogramming via Oxamate Targeting LDHA.International journal of molecular sciences · 2026Review
- Lactic Acid in Tumour Biology.Metabolites · 2026Review
- Immunosuppressive tumor microenvironment and immunotherapy resistance of esophageal carcinoma.Frontiers in immunology · 2026Review
- Mechanistic Research on the Crosstalk Between Macrophage Polarization and Energy Metabolic Reprogramming in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Review
- Identification and validation of prognostic genes related to glycolysis and M2 macrophage in hepatocellular carcinoma: an integrated analysis of bulk RNA sequencing and single-cell RNA sequencing.Frontiers in immunology · 2026Article
- Lactate at the crossroads of tumor metabolism and immune escape: a new frontier in cancer therapy.Journal of translational medicine · 2025Review
- Lymphoma accelerates T cell and tissue aging.Cancer cell · 2025Article
- Knockdown of LINC00467 inhibits gastric cancer progression by modulating the sequestration of miR-141-3p.Oncology letters · 2025Article
- Tumor microenvironment governs the prognostic landscape of immunotherapy for head and neck squamous cell carcinoma: A computational model-guided analysis.PLoS computational biology · 2025Article
- Review
- Sweet regulation - The emerging immunoregulatory roles of hexoses.Journal of advanced research · 2025Review
- Role of the AKT signaling pathway in regulating tumor-associated macrophage polarization and in the tumor microenvironment: A review.Medicine · 2025Review
- Prognostic and tumor microenvironmental features of gastric cancer revealed by macrophage polarization and protein lactylation-related genes.Frontiers in genetics · 2025Article
- Promotion of osteochondral repair through immune microenvironment regulation and activation of endogenous chondrogenesis via the release of apoptotic vesicles from donor MSCs.Bioactive materials · 2024Article
- Reprogramming Tumor-Associated Macrophage Using Nanocarriers: New Perspectives to Halt Cancer Progression.Pharmaceutics · 2024Review
- Current status of research on the mechanisms of tumor-associated macrophages in esophageal cancer progression.Frontiers in oncology · 2024Review
- Highly Selective MIF Ketonase Inhibitor KRP-6 Diminishes M1 Macrophage Polarization and Metabolic Reprogramming.Antioxidants (Basel, Switzerland) · 2023Article
- Lactate secreted by esophageal cancer cells induces M2 macrophage polarization via the AKT/ERK pathway.Thoracic cancer · 2023Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundElevated lactate results in an acidic tumor microenvironment (TME), which stimulates the progression of esophageal cancer (EC). Tumor-associated macrophages (TAMs) are an essential component of the TME. However, the regulatory mechanisms of lactate secreted by EC on TAMs and the effects of EC advancement are unclear.
methodsProteins and mRNA expression were determined by western blot and RT-qPCR. Cell metastasis and growth were assessed by scratch assay, transwell and BrdU assays. Lactate in cells was quantified using a lactate kit. A mouse model was constructed for validation in vivo.
resultsFirst, we determined that lactate upgraded the M2-type polarization marker levels of macrophages. Cell function assays confirmed that lactate-activated M2 macrophages accelerated EC cell migration and proliferation in vitro. However, the lactate inhibitor - oxamate hampered the level of lactate in TE-1 cells. Oxamate abolished the facilitation of macrophage polarization by lactate. In addition, we discovered that phosphorylated AKT and phosphorylated ERK was obviously raised in lactate-stimulated macrophages, and oxamate addition reversed this change, implying that AKT and ERK signaling pathways were involved in macrophage polarization. Response experiments proved that attenuation of AKT/ERK signaling markedly returned the lactate-induced promotion of EC migration and proliferation by macrophages. Finally, mouse tumor models demonstrated that lactate enhanced EC growth by inducing M2 macrophage polarization.
conclusionEC-secreted lactate stimulated macrophage M2 polarization via the AKT/ERK pathway thereby boosting the growth of EC.
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