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February 17, 2026Advanced ScienceOpen Access

UBE2T‐Driven p53 Degradation Rewires Glycolysis to Orchestrate Lactylation‐Mediated CAFs Activation and ECM Deposition in Pancreatic Cancer

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Authors

YMYide MaWLWei LiuMLMingdou Li

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Overview

Findings demonstrate UBE2T's role in promoting ECM deposition in PDAC, suggesting targeting UBE2T may improve immunotherapy efficacy.

Key Points

  • The study investigates how UBE2T contributes to lactate-mediated activation of cancer-associated fibroblasts in pancreatic cancer.
  • Utilized multi-omics and spontaneous cancer models.
  • Investigated the role of UBE2T in regulating p53 degradation.
  • Conducted genetic ablation and pharmacological inhibition using pentagalloylglucose (PGG).
  • Assessed effects on lactate metabolic crosstalk, ECM deposition, and immune cell infiltration.
  • Lactate accumulation in the tumor microenvironment promotes histone H3K18 lactylation and CAF activation.
  • UBE2T promotes p53 degradation, enhancing glycolysis and lactate production.
  • Inhibition of UBE2T disrupts lactate crosstalk and supports CD8+ T cells infiltration.
  • Combination therapy with PGG and anti-PD-1 shows synergistic effects and improved survival in models.

Cite This Study

Ma et al. (2026) studied this question.

synapsesocial.com/papers/699405bb4e9c9e835dfd694bhttps://doi.org/10.1002/advs.202514933
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Positive feedback regulation between glycolysis and histone lactylation drives oncogenesis in pancreatic ductal adenocarcinoma2024 · 382 citations
  2. 2Integrating metabolism and immunity: targeting lactate-mediated mechanisms in PDAC2026
  3. 3Targeting Lactate‐Driven Stromal Autophagy via MCT1 Disrupts the Immunosuppressive Niche and Sensitizes Pancreatic Cancer to PD‐1 Blockade2026
  4. 4Lactate metabolism reprogramming in PDAC: Potential for tumor therapy2025 · 18 citations
  5. 5Spatial transcriptomics reveals the mechanistic role of lactate metabolism in the pancreatic ductal adenocarcinoma microenvironment2026 · 2 citations