ArticleCommunications biology2025
Mannose inhibits PKM2 lactylation to induce pyroptosis in bladder cancer and activate antitumor immune responses.
Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Lactylation Remodels Tumorigenesis, Immune Microenvironment, and Therapeutic Response.Current issues in molecular biology · 2026Review
- Programmable engineered bacteria manipulate metabolism and remodel the TME in situ for enhancing adoptive cell therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- HNRNPU K181 Lactylation Drives Cervical Cancer Growth by Upregulating PHGDH and Reprogramming Serine Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lysine l-Lactylation: Bridging Metabolism, Chromatin and Disease.Cell proliferation · 2026Review
- Crosstalk between lactylation and other post-translational modifications in health and diseases.Molecular biomedicine · 2026Review
- Identification of pyroptosis-related molecular subtypes and development of a subtype-derived six-gene prognostic signature for bladder cancer.Translational andrology and urology · 2026Article
- Glycolytic lactylation modulates cell death decisions in diabetic kidney disease: Metabolic‑epigenetic interplay between ferroptosis and autophagy in fibrotic remodeling (Review).International journal of molecular medicine · 2026Review
- NEK2 drives pathogenesis, drug resistance, and LMP1 expression in EBV-positive non-Hodgkin lymphoma.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- FUT8 reprograms glycolytic metabolism to promote PKM2 lactylation and drive clear cell renal cell carcinoma progression.Cell death discovery · 2026Article
- The dual role of pyroptosis in prostate cancer: new perspectives from molecular mechanisms to clinical translation.Molecular biology reports · 2026Review
- [Advances in Lactate Metabolic Reprogramming in Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Unraveling the role of lactylation in cell death and correlative diseases: a comprehensive review.Frontiers in cell and developmental biology · 2026Review
- Aerobic glycolysis in bladder cancer: research advances and targeted therapy potential.Frontiers in oncology · 2026Review
- Programmed Cell Death in Urological Cancers: Orchestrating the Immune Microenvironment and Immunotherapy.Oncology research · 2026Review
- Role of lactylation modification in regulating lytic cell death.Frontiers in oncology · 2026Review
- Lactylation in urological malignancies: emerging mechanisms and therapeutic direction.Frontiers in cell and developmental biology · 2026Review
- Lactylation at the crossroads of immune metabolism and epigenetic regulation: revealing its role in rheumatic immune diseases.Journal of translational medicine · 2025Review
- Targeting Lactylation for Cancer: Mechanisms, Effects, and Therapeutic Prospects.International journal of molecular sciences · 2025Review
- Lactate at the crossroads of tumor metabolism and immune escape: a new frontier in cancer therapy.Journal of translational medicine · 2025Review
- Lactylation Modification and Aging: A Molecular Link in the Life Process.Aging and disease · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bladder cancer therapy remains challenging due to poor efficacy and frequent recurrence. Mannose, a naturally occurring monosaccharide, has demonstrated antitumor effects in various cancers, yet its mechanism of action in bladder cancer is unclear. This study explored the inhibitory effects of mannose on bladder cancer. We found mannose significantly inhibited the growth of bladder cancer cells, xenografts, and organoids. Mannose directly binds to PKM2, inhibiting its enzymatic activity and reducing lactate production. This reduction in lactate led to decreased PKM2 lactylation and increased acetylation, causing PKM2 to translocate to the nucleus. Nuclear PKM2 activated the NF-κB pathway, inducing NLRP1/Caspase-1/GSDMD/IL-1β-dependent pyroptosis. Additionally, mannose promoted antitumor immune responses by inducing pyroptosis and enhancing the efficacy of immune checkpoint inhibitors. These findings highlight the use of mannose as a potent antitumor agent and a promising therapeutic strategy for bladder cancer.
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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 Socratic graph.