ArticleCell death & disease2021
Lactate secreted by PKM2 upregulation promotes Galectin-9-mediated immunosuppression via inhibiting NF-κB pathway in HNSCC.
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 29 papers.
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Who cites it
29 citing papers in PubMed, 60 citations in OpenAlex.
- Understanding the epigenetic regulation of lactylation and aberrant lactate metabolism in cancer: From mechanisms to therapeutic strategies (Review).International journal of oncology · 2026Review
- Single-cell profiling reveals peripheral blood immune landscape remodelling in breast cancer lymph node metastasis.Clinical and translational medicine · 2026Article
- Microbial metabolic profiling reshapes NF-κB-mediated immune metabolic network: a new mechanism for CRC development.Journal of translational medicine · 2026Review
- PKM2 is the Metabolic Checkpoint for Stemness Features in Head and Neck Cancer.Journal of Cancer · 2026Article
- Article
- Molecular regulatory network of glycolytic reprogramming in hepatocellular carcinoma and its clinical implications.Biological procedures online · 2025Review
- Pathogenic role and therapeutic targets of nuclear factor-κB signaling pathway in cancer (Review).Oncology letters · 2025Review
- FTO enhances OSCC progression via m⁶A-dependent stabilization of PKM2 mRNA through YTHDF2 modulation.Head & face medicine · 2025Article
- Metformin combined with CB-839 specifically inhibits KRAS-mutant ovarian cancer.Scientific reports · 2025Article
- Targeting PKM2 in cancer therapeutics: mechanistic advances and translational opportunities.Frontiers in immunology · 2025Review
- Dendritic cell-based immunotherapy for head and neck squamous cell carcinoma: advances and challenges.Frontiers in immunology · 2025Review
- Immune-metabolic crosstalk in HNSCC: mechanisms and therapeutic opportunities.Frontiers in oncology · 2025Review
- SULT2B1: a novel therapeutic target in colorectal cancer via modulation of AKT/PKM2-mediated glycolysis and proliferation.Journal of translational medicine · 2024Article
- Bulk-RNA and single-nuclei RNA seq analyses reveal the role of lactate metabolism-related genes in Alzheimer's disease.Metabolic brain disease · 2024Article
- The regulatory roles and clinical significance of glycolysis in tumor.Cancer communications (London, England) · 2024Review
- Targeting histone deacetylases in head and neck squamous cell carcinoma: molecular mechanisms and therapeutic targets.Journal of translational medicine · 2024Review
- Knockdown of Ubiquitin-Conjugating Enzyme E2 T Abolishes the Progression of Head and Neck Squamous Cell Carcinoma by Inhibiting NF-Κb Signaling and inducing Ferroptosis.Current protein & peptide science · 2024Article
- The lactate metabolism and protein lactylation in epilepsy.Frontiers in cellular neuroscience · 2024Review
- PER2 binding to HSP90 enhances immune response against oral squamous cell carcinoma by inhibiting IKK/NF-κB pathway and PD-L1 expression.Journal for immunotherapy of cancer · 2023Article
- ESRRG-PKM2 axis reprograms metabolism to suppress esophageal squamous carcinoma progression and enhance anti-PD-1 therapy efficacy.Journal of translational medicine · 2023Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Pyruvate kinase M2 as a key rate-limiting enzyme in glycolysis, it plays a critical role in metabolic reprogramming and carcinogenesis. However, whether PKM2 can promote immunosuppressive microenvironment formation remains unknown in head and neck squamous cell carcinoma (HNSCC). PKM2 expression was detected using immunohistochemical staining. The biological functions of PKM2 were investigated in vitro and in vivo. Lactate production and the expression of Galectin-9, a critical immunosuppression molecule, were detected after PKM2 knockdown and overexpression in HNSCC cells. The mechanism of lactate regulating Galectin-9 expression through NF-κB signaling was explored in vitro. Overexpression of PKM2 correlates with poor prognosis in HNSCC patients. Silencing PKM2 markedly inhibits proliferation and metastasis capacity in vivo and in vitro, and vice versa. The glycolysis and glycolytic capacity are significantly decreased after PKM2 silencing. Lactate secretion induced by PKM2 significantly promotes migration and invasion capacity. Furthermore, a positive correlation between PKM2 and Galectin-9 expression is observed in HNSCC tissues. The induction of Galectin-9 expression by PKM2 can be affected by a lactate transporter inhibitor. Mechanically, lactate impeded the suppressive transcriptional complex formation of NF-κB and histone deacetylase 3 (HDAC3), which released the transcription of Galectin-9 mediated by NF-κB signaling. Our findings demonstrate that lactate produced by PKM2 upregulation promotes tumor progression and Galectin-9-mediated immunosuppression via NF-κB signaling inhibition in HNSCC, which bridges metabolism and immunosuppression. The novel PKM2-lactate-Galectin-9 axis might be a potential therapeutic target in HNSCC.
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Registered trials
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.