ArticleNature chemical biology2024
Tumor-repopulating cells evade ferroptosis via PCK2-dependent phospholipid remodeling.
Article in Nature chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Global trends in research of nasopharyngeal carcinoma: a bibliometric and visualization analysis.Frontiers in oncology · 2024Pooled it
- MMSDH facilitates ACSL4 propionylation to counteract ferroptosis upon hypoxia and impairs PDAC chemotherapy efficacy.Nature cancer · 2026Article
- PCK2 Inhibition Reverses Cisplatin Resistance of Non-Small Cell Lung Cancer by Triggering Ferroptosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- PCK2 Promotes Ribosome Biogenesis in Cervical Cancer Cells via Interaction with hnRNPK.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Chronic Exposure to Polystyrene Nanoplastics Promotes Lung Cancer Progression via Activating Gluconeogenesis and Inhibiting Glycolysis.Environment & health (Washington, D.C.) · 2026Article
- ACSL4 in Alzheimer's disease: Pathogenetic mechanisms and potential therapeutic targets.Genes & diseases · 2026Review
- Multidrug resistance in cancer: current understandings and future perspective.Molecular biomedicine · 2026Review
- Lipid metabolism reprogramming shapes the immune landscape in the tumor microenvironment.Cellular & molecular immunology · 2026Review
- Inducing Ferroptosis: Sensitization Strategy for Radiotherapy and Its Application.Antioxidants (Basel, Switzerland) · 2026Review
- Ferroptosis: unveiling a transformative perspective in the landscape of autoimmune diseases.Frontiers in immunology · 2026Review
- The macrophage polarization-ferroptosis axis as a therapeutically targetable immunometabolic framework in periodontitis.Frontiers in immunology · 2026Review
- NBR1-Mediated Autophagic Degradation of YTHDF1 CurtailsCancer communications (London, England) · 2026Article
- MRPS28 serves as a biomarker of diagnostic, prognostic, and immune modulation in pan-cancer and promotes breast cancer malignant phenotypes.Frontiers in immunology · 2026Article
- Elesclomol-Induced Copper Influx Attenuates Lung Adenocarcinoma Progression With Involvement of the ER Stress/PCK2 Axis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Targeting Ferroptosis in Nasopharyngeal Carcinoma: Mechanisms, Resistance, and Precision Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- Targeting cancer stem-like cells via cholesterol modulation and ferroptosis induction using a multifunctional nanoplatform to overcome drug resistance.Journal of nanobiotechnology · 2025Article
- Targeting ferroptosis in cancer stem cells: A novel strategy to improve cancer treatment.Genes & diseases · 2025Review
- From mitochondrial dysregulation to ferroptosis: Exploring new strategies and challenges in radioimmunotherapy (Review).International journal of oncology · 2025Review
- Ferroptosis in Cancer and Inflammatory Diseases: Mechanisms and Therapeutic Implications.MedComm · 2025Review
- Simvastatin overcomes the pPCK1-pLDHA-SPRINGlac axis-mediated ferroptosis and chemo-immunotherapy resistance in AKT-hyperactivated intrahepatic cholangiocarcinoma.Cancer communications (London, England) · 2025Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Whether stem-cell-like cancer cells avert ferroptosis to mediate therapy resistance remains unclear. In this study, using a soft fibrin gel culture system, we found that tumor-repopulating cells (TRCs) with stem-cell-like cancer cell characteristics resist chemotherapy and radiotherapy by decreasing ferroptosis sensitivity. Mechanistically, through quantitative mass spectrometry and lipidomic analysis, we determined that mitochondria metabolic kinase PCK2 phosphorylates and activates ACSL4 to drive ferroptosis-associated phospholipid remodeling. TRCs downregulate the PCK2 expression to confer themselves on a structural ferroptosis-resistant state. Notably, in addition to confirming the role of PCK2-pACSL4(T679) in multiple preclinical models, we discovered that higher PCK2 and pACSL4(T679) levels are correlated with better response to chemotherapy and radiotherapy as well as lower distant metastasis in nasopharyngeal carcinoma cohorts.
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Registered trials
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