ArticleNature communications2024
O-GlcNAcylation of MITF regulates its activity and CDK4/6 inhibitor resistance in breast cancer.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- O-GlcNAcylation Regulation of SNAP29-Dependent Autophagy Activation Dictates Chemoresistance in Gastric Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- MITF maintains genome stability in nonmelanocyte lineages.Molecular oncology · 2026Article
- Protein-encapsulated fluorogenic probes for the selective detection of endogenous O-GlcNAcase (OGA).Chemical science · 2026Article
- Identification ofFrontiers in pharmacology · 2026Article
- O-GlcNAcylation at the tumor-immune interface: a metabolic post-translational code driving immune evasion and therapy resistance in cancer.Frontiers in immunology · 2026Review
- Nuclear-Cytoplasmic Axis in Cancer: From Protein Mislocalization to Anticancer Drug Resistance.Oncology research · 2026Review
- Cancer-associated adipocytes confer CDK4/6 inhibitor resistance in ER+ breast cancer through an IL-6/STAT3/SREBF2 axis coupled with cholesterol metabolism and cell cycle reprogramming.International journal of biological sciences · 2026Article
- Targeting UAP1 with rabeprazole: a novel repurposed therapeutic strategy for multiple myeloma.Frontiers in pharmacology · 2026Article
- POFUT2 Mediated Fucosylation of JUP Enhances VEGFA Expression to Promote Angiogenesis in Colorectal Cancer.International journal of medical sciences · 2026Article
- Metabolic symbiosis and competition: the dual nature of TAM-tumor cell cross-talk in tumor progression.Frontiers in oncology · 2026Review
- Lidocaine suppresses HER2-positive breast cancer cell proliferation by targeting the OGT-CCNL1 axis.Discover oncology · 2025Article
- METTL10-Mediated PIAS3 Methylation Links Purine Metabolism to Gastric Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cell cycle regulation in cancer cells by O-GlcNAcylation.Glycoconjugate journal · 2025Review
- MITF regulates autophagy and extracellular vesicle cargo in gastrointestinal stromal tumors.Molecular biomedicine · 2025Article
- And-1 coordinates with polymerase δ to regulate nucleotide excision repair and UVB-induced skin tumorigenesis.Nature communications · 2025Article
- Cerium oxide-embedded gold nanoparticles loaded with astragaloside IV for bladder cancer therapy.Scientific reports · 2025Article
- High-throughput transcriptomics analysis of equipotent and human relevant mixtures of BPA alternatives reveal additive effects in vitro.Archives of toxicology · 2025Article
- Prognostic and therapeutic implications related to glycosylation profiles of cancer-associated fibroblasts in colorectal cancer: insights from single-cell and bulk transcriptomics.Functional & integrative genomics · 2025Article
- O-GlcNAcylation of METTL3 drives hepatocellular carcinoma progression by upregulating MCM10 expression in an m6A-IGF2BP3-dependent manner.Cell death & disease · 2025Article
- Preclinical study of microphthalmia-associated transcription factor inhibitor ML329 in gastrointestinal stromal tumor growth.Molecular therapy. Oncology · 2025Article
Corrections and comments
- Erratum issued
- Update of
Authors and funding
15 authors.
Funding
Abstract
Cyclin-dependent kinases 4 and 6 (CDK4/6) play a pivotal role in cell cycle and cancer development. Targeting CDK4/6 has demonstrated promising effects against breast cancer. However, resistance to CDK4/6 inhibitors (CDK4/6i), such as palbociclib, remains a substantial challenge in clinical settings. Using high-throughput combinatorial drug screening and genomic sequencing, we find that the microphthalmia-associated transcription factor (MITF) is activated via O-GlcNAcylation by O-GlcNAc transferase (OGT) in palbociclib-resistant breast cancer cells and tumors. Mechanistically, O-GlcNAcylation of MITF at Serine 49 enhances its interaction with importin α/β, thus promoting its translocation to nuclei, where it suppresses palbociclib-induced senescence. Inhibition of MITF or its O-GlcNAcylation re-sensitizes resistant cells to palbociclib. Moreover, clinical studies confirm the activation of MITF in tumors from patients who are palbociclib-resistant or undergoing palbociclib treatment. Collectively, our studies shed light on the mechanism regulating palbociclib resistance and present clinical evidence for developing therapeutic approaches to treat CDK4/6i-resistant breast cancer patients.
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