ArticleCellular and molecular gastroenterology and hepatology2022
Hyperglycemia Enhances Immunosuppression and Aerobic Glycolysis of Pancreatic Cancer Through Upregulating Bmi1-UPF1-HK2 Pathway.
Article in Cellular and molecular gastroenterology and hepatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 62 citations in OpenAlex.
- Malignant Transformation Risk in Patients With Oral Leukoplakia and Type 2 Diabetes Mellitus.International dental journal · 2026Article
- Impact of good glycemic control on survival of pancreatic ductal adenocarcinoma with diabetes mellitus.BMC gastroenterology · 2026Article
- Exploring the role of metabolic disorders and gut microbiome in immune checkpoint regulation in cancer: PI3K/AKT/mTOR focus.Journal of physiology and biochemistry · 2026Review
- Review
- Causal relationship between metabolic syndrome and gastric cancer: insights from comprehensive analysis and biomarker identification.Translational cancer research · 2026Article
- HK2 drives synaptic dysfunction in fragile X syndrome via epigenetic regulation of H3K18 lactylation.Frontiers in pharmacology · 2026Article
- UPF1-dependent glycolysis driven by LINC00887 facilitates macrophage M2 polarization in clear cell renal cell carcinoma.Frontiers in immunology · 2026Article
- Unraveling Diabetes Mellitus-Driven Tumorigenesis: From Pathophysiological Mechanisms, Therapeutic Drugs to Tailor-Made Nanosystems.International journal of nanomedicine · 2026Review
- Bridging diabetes and cancer: harnessing biomarkers as dual sentinels for diagnosis, prognosis, and therapeutic advancements.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Immunometabolism: crosstalk with tumor metabolism and implications for cancer immunotherapy.Molecular cancer · 2025Review
- diPaRIS: Dynamic and Interpretable Protein-RNA Interactions Prediction With U-Shaped Network and Novel Structure Encoding.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- Establishing a glycolysis-linked multigene prognostic signature in lung adenocarcinoma: a multicenter integrative approach.Journal of thoracic disease · 2025Article
- Glioma stem cells: drivers of tumor progression and recurrence.Stem cell research & therapy · 2025Review
- Tumor-associated macrophages (TAMs): Constructing an immunosuppressive microenvironment bridge for pancreatic ductal adenocarcinoma (PDAC).Cancer pathogenesis and therapy · 2025Review
- Dysbiosis-NK Cell Crosstalk in Pancreatic Cancer: Toward a Unified Biomarker Signature for Improved Clinical Outcomes.International journal of molecular sciences · 2025Review
- Reprogramming of glucose metabolism in pancreatic cancer: mechanisms, implications, and therapeutic perspectives.Frontiers in immunology · 2025Review
- Metabolic and Immunological Implications of MMEBiological procedures online · 2024Article
- Single-cell transcriptome analysis revealed heterogeneity in glycolysis and identified IGF2 as a therapeutic target for ovarian cancer subtypes.BMC cancer · 2024Article
- Bidirectional relationship between pancreatic cancer and diabetes mellitus: a comprehensive literature review.Annals of medicine and surgery (2012) · 2024Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsAccumulating evidence strongly suggests that hyperglycemia promotes the progression of pancreatic cancer (PC). Approximately 80% of patients with PC are intolerant to hyperglycemic conditions. In this study, we define the role of Bmi1, a stemness-related oncogene, in controlling the Warburg effect, and immune suppression under hyperglycemia conditions.
methodsThe diabetes mellitus model was established by intraperitoneal injection of streptozotocin. The role of the hyperglycemia-Bmi1-HK2 axis in glycolysis-related immunosuppression was examined in both orthotopic and xenograft in vivo models. Evaluation of immune infiltrates was carried out by flow cytometry. Human PC cell lines, SW1990, BxPC-3, and CFPAC-1, were used for mechanistic in vitro studies.
resultsThrough bioinformatics analysis, we found that hyperglycemia was strongly related to aerobic glycolysis, immunosuppression, and cancer cell stemness. High glucose condition in the tumor microenvironment promotes immune suppression by upregulating glycolysis in PC cells, which can be rescued via knockdown Bmi1 expression or after 2-deoxy-D-glucose treatment. Through gain-/loss-of-function assessments, we found that Bmi1 upregulated the expression of UPF1, which enhanced the stability of HK2 mRNA and thereby increased the expression of HK2. The role of the hyperglycemia-Bmi-HK2 pathway in the inhibition of antitumor immunity was further verified via the immune-competent and immunodeficient mice model. We also demonstrated that hyperglycemia promotes the expression of Bmi1 by elevating the intracellular acetyl-CoA levels and histone H4 acetylation levels.
conclusionsOur results suggest that the previously unreported Bmi1-UPF1-HK2 pathway contributes to PC progression and immunosuppression, which may bring in new targets for developing effective therapies to treat patients with PC.
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