ArticleCancer science2025
Exosomal PKM2: A Noninvasive Diagnostic Marker Linking Macrophage Metabolic Reprogramming to Gastric Cancer Pathogenesis.
Article in Cancer science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Review
- The evolving landscape of the Warburg effect in gastric cancer: From molecular mechanisms to targeted therapy.Clinical and translational medicine · 2026Review
- Single-cell and spatial transcriptomes reveal oligodendrocyte remodeling fatty acid metabolism microenvironment of lung cancer brain metastases.Journal of translational medicine · 2026Article
- Targeting Pyruvate Kinase M2: Signal Transduction Pathways and Exploration of Cancer Therapeutic Strategies.The AAPS journal · 2026Review
- Metabolic regulation of tumor-associated macrophage function and immunotherapy in cancer.Cancer biology & medicine · 2026Review
- Exosome-orchestrated network in gastric cancer: mechanisms, immune regulation, biomarkers and therapeutic vehicles.Frontiers in cell and developmental biology · 2026Review
- Exosome-Mediated Macrophage Polarization in Gastric Cancer: Inflammatory and Neuroinflammatory Mechanisms and Therapeutic Potential.International journal of general medicine · 2026Review
- Exosome-mediated metabolic-immune regulatory axis: mechanisms of gastric cancer progression and resistance and targeting strategies.Frontiers in immunology · 2026Review
- Effect of PKM2 onFrontiers in cellular and infection microbiology · 2026Article
- Precision Thyroid Oncology: A Review of Multi-Omics Biomarkers and Spatiotemporal Technologies.International journal of general medicine · 2026Review
- Exosomes in Clinical Laboratory: From Biomarker Discovery to Diagnostic Implementation.Medicina (Kaunas, Lithuania) · 2025Review
- Recent progress in the study of exosomes in the gastric cancer immune microenvironment.Frontiers in immunology · 2025Review
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Authors and funding
11 authors.
Funding
Abstract
Tumor-derived exosomes (TDEs) have emerged as vital biomarkers of multiple cancers. However, the diagnostic and stage-predicting effects of exosomal pyruvate kinase isoenzyme type M2 (PKM2) in peripheral blood and its mechanism in promoting gastric cancer (GC) remain unclear. Here, we analyzed plasma exosomal PKM2 in 216 blood samples collected from GC patients and healthy donors (HD). The area under the curve (AUC) of plasma exosomal PKM2 demonstrated superior performance in early GC diagnosis compared with that of widely used clinical biomarkers. Kaplan-Meier analysis revealed that high exosomal PKM2 expression was associated with poor prognosis in patients with GC (HR = 1.623, p = 0.029). Single-cell transcriptome sequencing analysis showed that PKM2 was enriched in tumor-associated macrophages (TAM). We further confirmed that the polarization of TAM to the pro-tumoral M2 phenotype induced by exosomal PKM2 promoted the proliferation, migration, and invasion of GC cells. Mechanistically, exosomal PKM2 enhanced lipid synthesis in TAM by inhibiting SCAP polyubiquitination, which triggered the nuclear accumulation of SREBP1, thereby upregulating fatty acid synthesis enzymes, such as FASN, ACACA, and ACLY. In conclusion, plasma exosomal PKM2 is a promising novel biomarker for the clinical diagnosis of GC. Importantly, exosomal PKM2 shapes the tumor microenvironment by activating the SREBP1-related lipid synthesis pathway in macrophages, thereby contributing to GC development.
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