ArticleCell death and differentiation2025
Lactylation-driven USP4-mediated ANXA2 stabilization and activation promotes maintenance and radioresistance of glioblastoma stem cells.
Article in Cell death and differentiation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Targeting the BMX in cancer: molecular mechanisms and emerging therapeutic strategies.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Persistent ZnAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Annexin A2 associated with bevacizumab resistance and infiltrative escape in glioblastoma.Journal of neuro-oncology · 2026Article
- Metabolic Reprogramming in Glioblastoma Stem Cells Promotes Radiation Resistance Through a H3K18la/USP30/MBOAT2 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Unveiling Lactylation: A Novel Frontier in Cancer Stemness and Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Lysine l-Lactylation: Bridging Metabolism, Chromatin and Disease.Cell proliferation · 2026Review
- The role of Annexin A2 in Alzheimer's disease: From cellular functions to therapeutic potential.The FEBS journal · 2026Review
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- SerpinB7 promotes c-Myc-mediated glycolysis by interacting with ANXA2 to facilitate the progression of non-small cell lung cancer.Molecular cancer · 2026Article
- Thr3/Ser90 phosphorylation-stabilized S100A8 regulates cholesterol metabolism in glioblastoma stem cells.Oncogene · 2026Article
- CEMs-SELEX: DNAzyme-powered de novo biomarker discovery and noninvasive cancer diagnosis.Science advances · 2026Article
- Protein lactylation: a metabolic signal driving cancer therapy resistance.Cell death discovery · 2026Review
- Dysregulation of post-translational modifications in glioma: advances in pathological mechanisms and clinical targeting strategies.Journal of translational medicine · 2026Review
- Glycolysis enzymes and cellular lactylation in tumour.Clinical and translational medicine · 2026Review
- Exercise-specific post-translational modification signatures: unveiling precise regulatory mechanisms of molecular exercise language and cellular adaptation.Frontiers in sports and active living · 2026Review
- Histone H4K8 lactylation promotes glioblastoma progression by inducing NUPR1-mediated autophagosome‒lysosome fusion.Theranostics · 2026Article
- Acetylation modification in malignant progression and therapeutic resistance of gliomas.Frontiers in cell and developmental biology · 2026Review
- Regulatory roles of five key USP family deubiquitinases in cancer: from mechanisms to targeted therapy advances.Frontiers in pharmacology · 2026Review
- The MCU-MECOM Axis Orchestrates Glioblastoma Progression by Remodeling Mitochondrial Dynamics and Quality Control via MAMs.International journal of biological sciences · 2026Article
- Protein lactylation: molecular mechanisms underlying lactate-driven tumorigenesis and cancer progression.Cancer biology & therapy · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
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Abstract
Glioblastoma (GBM) is the most primary lethal brain cancer, characterized by the presence of glioblastoma stem cells (GSCs) that initiate and sustain tumor growth and induce radioresistance. Annexin A2 (ANXA2) has been reported to contribute to glioblastoma progression and impart stem cell-like properties to GSCs, however, its post-translational modifications and mechanisms in GSCs maintenance remain poorly understood. Here, we identify that USP4 is preferentially expressed by GSCs in GBM, USP4/ANXA2 supports GSCs maintenance and radioresistance. Specifically, USP4 interacts with ANXA2, stabilizing its protein by deubiquitinating ANXA2, which mediates its proteasomal degradation and Y24 phosphorylation. USP4 directly cleaves Lys48- and Lys63-linked polyubiquitin chains of ANXA2, with the Lys63-linked polyubiquitin chains of ANXA2 K28 mediating its Y24 phosphorylation. Moreover, K10 acetylation of ANXA2 enhances its interaction with USP4. Importantly, USP4/ANXA2 promotes GSCs maintenance and radioresistance by activating BMX-mediated STAT3 activation. H3K18 lactylation is responsible for the upregulation of USP4 in GSCs. Our studies reveal that USP4/ANXA2 plays critical roles in maintaining GSCs and therapeutic resistance, highlighting the importance of lactylation, acetylation, ubiquitination, and phosphorylation as critical post-translational modifications for USP4-mediated stabilization and activity of ANXA2.
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