ArticleCell death discovery2023
Drug-induced lactate confers ferroptosis resistance via p38-SGK1-NEDD4L-dependent upregulation of GPX4 in NSCLC cells.
Article in Cell death discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Ferroptosis in chemotherapy resistance and resensitization in breast cancer: a systematic review of preclinical evidence and translational implications.Frontiers in oncology · 2026Pooled it
- Research progress on lactate metabolism in lung cancer: Tumorigenesis, drug resistance and clinical translation (Review).Oncology reports · 2026Review
- Ferroptosis-Pyroptosis Crosstalk in Spinal Cord Injury: Molecular Mechanisms, Emerging Connectors, and Staged Therapeutic Perspectives.Journal of molecular neuroscience : MN · 2026Review
- NRF2 activation is required for chemotherapy resistance acquisition in medulloblastoma via metabolic and redox adaptation.Redox biology · 2026Article
- Selenoprotein thioredoxin reductase 1 promotes cancer cells ferroptosis by suppressing GPX4 expression.Cell death and differentiation · 2026Article
- Lactate-dependent regulation of ferroptosis: redox homeostasis, lactylation, and translational perspectives.Apoptosis : an international journal on programmed cell death · 2026Review
- Usnic acid inhibits colorectal cancer liver metastasis by targeting CRYAB phosphorylation and inducing ferroptosis.Cell communication and signaling : CCS · 2026Article
- Lactylation of β-catenin promotes non-small cell lung cancer by inhibiting ferroptosis through TCF4-mediated GPX4 transcription.Journal of translational medicine · 2026Article
- Dual role of lactate in ferroptosis: Mechanisms, pathophysiology and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- PDIA3 Inhibition Facilitates Sensitivity of IKE-Induced Ferroptosis via STAT3/LCN2 Axis to Improve Glioblastoma Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Beyond metabolism: exploring the regulatory and therapeutic implications of lactate and lactylation in cancer-regulated cell death.Cell death & disease · 2026Review
- Article
- Exercise-Induced Lactate Is Associated with the Modulation of Mitophagy and Ferroptosis and Reduced Amyloid-Beta and Tau in Type 2 Diabetes.Iranian biomedical journal · 2026Article
- Targeting glutathione peroxidase 4 in ferroptosis: from immune regulation to pharmacological development and translational applications.Frontiers in pharmacology · 2026Review
- Potential Mechanisms of Exercise-Mediated Ferroptosis Regulation in Central Nervous System Diseases.Molecular neurobiology · 2025Review
- Targeted ferroptosis induction enhances chemotherapy efficacy in chemoresistant neuroblastoma.NPJ precision oncology · 2025Article
- Review
- NEDD4L-Mediated Ubiquitination of GPX4 Exacerbates Doxorubicin-Induced Cardiotoxicity.International journal of molecular sciences · 2025Article
- The Regulation of Trace Metal Elements in Cancer Ferroptosis.Advanced biology · 2025Review
- Modulation of ferroptosis via YY1-SLC7A11 axis in hepatic ischemia-reperfusion injury pathogenesis.Acta biochimica et biophysica Sinica · 2025Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Ferroptosis is a newly defined non-apoptotic programmed cell death resulting from the accumulation of lipid peroxides. Whether ferroptosis plays any role in chemotherapy remains to be established. Here, we reported that ferroptosis represents a part of the chemotherapeutic drug etoposide-induced cell death response in Small Cell Lung Cancer (SCLC) cells and adaptive signaling molecule lactate protects Non-Small Cell Lung Cancer (NSCLC) from etoposide-induced ferroptosis. Lactate derived from metabolic reprogramming increases the expression of glutathione peroxidase 4 (GPX4) to promote ferroptosis resistance in NSCLC. Furthermore, we identified E3-ubiquitin ligase NEDD4L as a major regulator of GPX4 stability. Mechanistically, Lactate increases mitochondrial ROS generation and drives activation of the p38-SGK1 pathway, which attenuates the interaction of NEDD4L with GPX4 and subsequent ubiquitination and degradation of GPX4. Our data implicated the role of ferroptosis in chemotherapeutic resistance and identified a novel post-translational regulatory mechanism for the key Ferroptosis mediator GPX4.
Identifiers
What OpenQuestion holds
Registered trials
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.