ArticleNature communications2023
Lysyl oxidase-like 3 restrains mitochondrial ferroptosis to promote liver cancer chemoresistance by stabilizing dihydroorotate dehydrogenase.
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 57 papers, 1 of them a synthesis that pooled it.
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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
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Redox-manipulating nanocarriers for anticancer drug delivery: a systematic review.Journal of nanobiotechnology · 2024Pooled it
- Ferroptosis in liver biology and diseases.Hepatology communications · 2026Review
- Piezoelectric Nanozymes With Acoustically Rejuvenated Catalytic Activities Rewire Lipid Metabolism for Two-Pronged Ferroptotic Therapy.Angewandte Chemie (International ed. in English) · 2026Article
- DHODH-Mediated Suppression of Ferroptosis Supports Radioresistance and Represents a Therapeutic Vulnerability in Lung Cancer.Cancer research · 2026Article
- Low-dose EGFR inhibition unlocks ferroptosis susceptibility to sensitize chemotherapy in EGFR-high triple-negative breast cancer.The Journal of biological chemistry · 2026Article
- Targeting the 4EBP1/HSP90β/Nrf2 Axis Sensitizes β-catenin-mutant Hepatocellular Carcinoma to mTOR Inhibitors via Ferroptosis Induction.Journal of clinical and translational hepatology · 2026Article
- Mitochondrial-Localized Keratin 17 Promotes Chemoresistance in Basal-like Pancreatic Cancer.Cancer research · 2026Article
- Syringin disrupts the DLAT/MYC axis to dampen TAM polarization and suppress hepatocellular carcinoma progression.Acta pharmaceutica Sinica. B · 2026Article
- Genetic mutations governing ferroptosis sensitivity and resistance: a precision approach to cancer therapy.Cell death & disease · 2026Review
- Ferroptosis in Neuropsychiatric and Neurodegenerative Disorders: Shared Mechanisms and Disease-Specific Signatures.Pharmaceuticals (Basel, Switzerland) · 2026Review
- RRx-001 inhibits G6PD to deplete NADPH and trigger disulfidptosis coupled with DAMP-mediated immunogenic cell death in hepatocellular carcinoma.Cell death discovery · 2026Article
- Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Ferroptosis: The dawn of reversing drug resistance in digestive cancers.Genes & diseases · 2026Review
- VAMP7 governs ferroptosis suppression and cisplatin resistance in esophageal cancer: a dual-targeting therapeutic paradigm.Cancer cell international · 2026Article
- Article
- Long noncoding RNA PCAT7 confers radioresistance of esophageal squamous cell carcinoma by promoting GCLM-mediated anti-ferroptosis.Journal of translational medicine · 2026Article
- Post-translational modifications in ferroptosis: mechanisms and therapeutic potential.International journal of biological sciences · 2026Review
- Exploring the role of adenosine deaminase in esophageal cancer and its potential for traditional Chinese medicine intervention.Frontiers in molecular biosciences · 2026Article
- Exploiting metabolic cell death for cancer therapy.Nature reviews. Cancer · 2026Review
- Post-translational modification in hepatocellular carcinoma resistance: molecular mechanisms and therapeutic targeting.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To overcome chemotherapy resistance, novel strategies sensitizing cancer cells to chemotherapy are required. Here, we screen the lysyl-oxidase (LOX) family to clarify its contribution to chemotherapy resistance in liver cancer. LOXL3 depletion significantly sensitizes liver cancer cells to Oxaliplatin by inducing ferroptosis. Chemotherapy-activated EGFR signaling drives LOXL3 to interact with TOM20, causing it to be hijacked into mitochondria, where LOXL3 lysyl-oxidase activity is reinforced by phosphorylation at S704. Metabolic adenylate kinase 2 (AK2) directly phosphorylates LOXL3-S704. Phosphorylated LOXL3-S704 targets dihydroorotate dehydrogenase (DHODH) and stabilizes it by preventing its ubiquitin-mediated proteasomal degradation. K344-deubiquitinated DHODH accumulates in mitochondria, in turn inhibiting chemotherapy-induced mitochondrial ferroptosis. CRISPR-Cas9-mediated site-mutation of mouse LOXL3-S704 to D704 causes a reduction in lipid peroxidation. Using an advanced liver cancer mouse model, we further reveal that low-dose Oxaliplatin in combination with the DHODH-inhibitor Leflunomide effectively inhibit liver cancer progression by inducing ferroptosis, with increased chemotherapy sensitivity and decreased chemotherapy toxicity.
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