ArticleCell death & disease2021
The role of PKM2 nuclear translocation in the constant activation of the NF-κB signaling pathway in cancer-associated fibroblasts.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 103 citations in OpenAlex.
- Metabolic heterogeneity and functional diversity of cancer-associated fibroblasts in gastric cancer (Review).Oncology letters · 2026Review
- The evolving landscape of the Warburg effect in gastric cancer: From molecular mechanisms to targeted therapy.Clinical and translational medicine · 2026Review
- RPS5 modulates inflammatory response and angiogenesis in coronary heart disease through NF-κB signaling activation.Molecular and cellular biochemistry · 2026Article
- TRIM47 promotes cell viability, cell cycle progression, metabolic reprogramming, and inhibits apoptosis of glioma via the NF-κB signaling pathway.Translational cancer research · 2026Article
- Emerging agents that target signaling pathways in cancer fibroblast cells (Review).International journal of oncology · 2026Review
- Targeting Pyruvate Kinase M2: Signal Transduction Pathways and Exploration of Cancer Therapeutic Strategies.The AAPS journal · 2026Review
- Upregulated PKM2 Protects Dopaminergic Neurons From Oxidative Damage Through Nrf2 Transactivation in an MPTP-Induced Mouse Model of Parkinson's Disease.CNS neuroscience & therapeutics · 2026Article
- STK25 inhibits cancer-associated fibroblast activation to overcome cetuximab resistance in colorectal cancer.Clinical and translational medicine · 2026Article
- Deciphering autophagy-metabolism interactions in cancer drug resistance: a comprehensive review.Cancer chemotherapy and pharmacology · 2026Review
- Targeting Glycolytic Metabolism in Cancer Therapy: Current Approaches and Future Perspectives.Cells · 2026Review
- Exosome-mediated metabolic-immune regulatory axis: mechanisms of gastric cancer progression and resistance and targeting strategies.Frontiers in immunology · 2026Review
- Cancer-Associated Fibroblasts in Gastrointestinal Cancer Metastasis: Mechanisms and Emerging Therapeutic Strategies.Drug design, development and therapy · 2026Review
- Harnessing the power of cancer-associated fibroblasts to revolutionize pancreatic cancer treatment.Cancer biology & medicine · 2025Review
- Single-cell transcriptomic analysis reveals distinct cancer-associated fibroblast signatures in treatment-refractory esophageal squamous cell carcinoma.Scientific reports · 2025Article
- Transient overexpression of hPKM2 in porcine cardiomyocytes prevents heart failure after myocardial infarction.Nature communications · 2025Article
- Review
- PCBP1-AS1 facilitates liver metastasis in pancreatic cancer by modulating miR-125b-5p in Tumor-derived exosomes to target TNFAIP3.BMC cancer · 2025Article
- TUBB3 (βIII-tubulin) drives gastric cancer progression and poor prognosis by regulating cell cycle and invadopodia formation.Cancer biomarkers : section A of Disease markers · 2025Article
- Autophagy inhibition improves the efficacy of anlotinib and PD-1 inhibitors in the treatment of NSCLC.Journal for immunotherapy of cancer · 2025Article
- The Underlying Mechanisms and Emerging Strategies to Overcome Resistance in Breast Cancer.Cancers · 2025Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer-associated fibroblasts (CAFs) play critical roles in cancer progression by regulating tumor cell proliferation, angiogenesis, and metastasis. Recent studies demonstrated that CAFs induce inhibitory immune cell infiltration and chemotherapy resistance in gastric cancer by activating the NF-κB signaling pathway to secrete IL6, IL8, and other inflammatory factors. Inhibition of the NF-κB signaling pathway in CAFs might be a potential therapeutic strategy in gastric cancer. However, how the NF-κB pathway is activated in CAFs remains unclear. We showed that mesenchymal stem cells (MSCs) differentiated into CAFs, induced by the exosomes derived from gastric cancer cells. During the process of differentiation from MSCs into CAFs, we showed that nuclear PKM2 expression was continuously upregulated and associated with NF-κB P65 acetylation, contributing to P65 nuclear retention in CAFs and constant transcription of IL-6, IL-8, and other inflammatory factors, thus promoting gastric cancer cell proliferation. We showed that NF-κB P65 acetylation was induced by P300. We showed that nuclear PKM2 was derived from exosomes of gastric cancer cell lines and the positive feedback loop induced by PKM2-P65 combination. It is also proved that P300 inhibitors can inhibit tumor proliferation in an AGS subcutaneous xenograft tumor model. Our study showed that gastric cancer cells influence the continuous activation of the NF-κB signaling pathway in CAFs by secreting gastric cancer exosomes containing PKM2, thus inducing abnormal metabolism and inflammation activation. This study provides a new therapeutic target for CAF normalization or deactivation strategies.
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