ArticleNature communications2023
Lysine methylation promotes NFAT5 activation and determines temozolomide efficacy in glioblastoma.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Review
- The mitochondrial translocation of phosphorylated EZH2 promotes PARP inhibitor resistance in BRCA1-deficient epithelial ovarian cancer.Cell discovery · 2026Article
- Kidney-Tonifying, Phlegm-Resolving, and Blood Stasis-Removing Therapy for Multiple Myeloma: Protocol for a Randomized Controlled Trial on Epigenetic and Immune Modulation.JMIR research protocols · 2026Article
- High-salt diet aggravates allergic rhinitis through the NFAT5 signaling pathway.NPJ science of food · 2026Article
- Co-activation of the super-enhancer complex SOX2 and HDAC1 confers temozolomide resistance by promoting PDGFB transcription in glioblastoma.Neuro-oncology · 2026Article
- Association of NDRG4 gene methylation in peripheral blood leukocytes with gastric cancer risk, chemotherapy efficacy and prognosis.Frontiers in oncology · 2026Article
- The BRAF V600E/MEK/ERK/METTL3 positive feedback loop regulates autophagy and promotes stemness and invasiveness in glioblastoma via mJournal of experimental & clinical cancer research : CR · 2025Article
- E3 ubiquitin ligase BTRC inhibits the proliferation and tumor growth of glioma cells through the NFAT5/AQP4 axis.Journal of cancer research and clinical oncology · 2025Article
- Role of lysine acetylation-related genes in the diagnosis and prognosis of glioma.Scientific reports · 2025Article
- Overcoming temozolomide resistance in glioma: recent advances and mechanistic insights.Acta neuropathologica communications · 2025Review
- Post-translational modifications in DNA damage repair: mechanisms underlying temozolomide resistance in glioblastoma.Oncogene · 2025Review
- 5-Methylcytosine RNA modification and its roles in cancer and cancer chemotherapy resistance.Journal of translational medicine · 2025Review
- NFAT5 exacerbates β-cell ferroptosis by suppressing the transcription of PRDX2 in obese type 2 diabetes mellitus.Cellular and molecular life sciences : CMLS · 2025Article
- NFAT5 governs cellular plasticity-driven resistance to KRAS-targeted therapy in pancreatic cancer.The Journal of experimental medicine · 2024Article
- Radiogenomics as an Integrated Approach to Glioblastoma Precision Medicine.Current oncology reports · 2024Review
- Preparation of transferrin-targeted temozolomide nano-micelles and their anti-glioma effect.PeerJ · 2024Article
- Research progress on S-palmitoylation modification mediated by the ZDHHC family in glioblastoma.Frontiers in cell and developmental biology · 2024Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Temozolomide (TMZ) therapy offers minimal clinical benefits in patients with glioblastoma multiforme (GBM) with high EGFR activity, underscoring the need for effective combination therapy. Here, we show that tonicity-responsive enhancer binding protein (NFAT5) lysine methylation, is a determinant of TMZ response. Mechanistically, EGFR activation induces phosphorylated EZH2 (Ser21) binding and triggers NFAT5 methylation at K668. Methylation prevents NFAT5 cytoplasm interaction with E3 ligase TRAF6, thus blocks NFAT5 lysosomal degradation and cytosol localization restriction, which was mediated by TRAF6 induced K63-linked ubiquitination, resulting in NFAT5 protein stabilization, nuclear accumulation and activation. Methylated NFAT5 leads to the upregulation of MGMT, a transcriptional target of NFAT5, which is responsible for unfavorable TMZ response. Inhibition of NFAT5 K668 methylation improved TMZ efficacy in orthotopic xenografts and patient-derived xenografts (PDX) models. Notably, NFAT5 K668 methylation levels are elevated in TMZ-refractory specimens and confer poor prognosis. Our findings suggest targeting NFAT5 methylation is a promising therapeutic strategy to improve TMZ response in tumors with EGFR activation.
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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 OpenQuestion graph.