ArticleMolecular cell2023
Lysosomal cystine governs ferroptosis sensitivity in cancer via cysteine stress response.
Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 62 citations in OpenAlex.
- SLC3A1 Mitigates Ferroptosis and Promotes Enzalutamide Resistance in Prostate Cancer.Journal of biochemical and molecular toxicology · 2026Article
- ATF4 orchestrates cancer hallmarks: Stress adaptation, metabolic reprogramming and immune suppression.iScience · 2026Review
- MAPK Inhibitor-Tolerant Persister Cells in Melanoma: Mechanisms and Therapeutic Vulnerabilities.Cancer science · 2026Review
- Lysosomes in Ferroptosis: Regulatory Mechanisms and Molecular Targets.Molecules (Basel, Switzerland) · 2026Review
- FerroScore: a statistical approach for quantifying tumor-related ferroptosis based on omics data.Briefings in bioinformatics · 2026Article
- Lysosome-derived methylated arginine is a signalling metabolite controlling the lipidome.Nature cell biology · 2026Article
- Targeting ATF4 overcomes dual resistance to chemo-immunotherapy in gastric cancer by disrupting the DNA damage response.Journal for immunotherapy of cancer · 2026Article
- Dose- and time-dependent cardioprotection of liproxstatin-1 via sequential modulation of ferroptosis pathways after myocardial ischemia-reperfusion.Molecular and cellular biochemistry · 2026Article
- Translating ferroptosis into oncology: challenges, opportunities and future directions.Nature reviews. Clinical oncology · 2026Review
- The integrated stress response in cancer: mechanisms of tumor adaptation and therapeutic targeting.Biochemical Society transactions · 2026Review
- Application of a novel myristoylproteomics approach identifies GLIPR2 as a key pro-ferroptotic substrate in non-small cell lung cancer.Materials today. Bio · 2026Article
- TDG orchestrates ATF4-dependent gene transcription during retinoic acid-induced cell fate acquisition.Nucleic acids research · 2026Article
- Multi-layered integrated shielding: engineering ferroptosis-resistant mesenchymal stem cells for precision therapy of intervertebral disc degeneration.Apoptosis : an international journal on programmed cell death · 2026Review
- Fueling Death: The Metabolic Control of Ferroptosis.Advances in experimental medicine and biology · 2026Review
- Aryl hydrocarbon receptor regulates programmed cell death in diseases: molecular mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Long Non-Coding RNA PVT1 Promotes Doxorubicin Resistance by Inhibiting Ferroptosis in Breast Cancer.Breast cancer (Dove Medical Press) · 2026Article
- Drug-Induced Glucose Metabolism Disorders: Role of Aryl Hydrocarbon Receptor.Journal of xenobiotics · 2025Review
- Targeting ferroptosis as a therapeutic strategy for hepatotoxicity.Toxicology reports · 2025Review
- Single-cell transcriptomics uncovering a critical AKT-LONP1-STAR axis in ovarian hyperandrogenism of PCOS.Journal of ovarian research · 2025Article
- Chr:17q21.31 locus risk haplotype H1 susceptibility to ferroptosis is mediated by endolysosomal pathway.Cell death & disease · 2025Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The amino acid cysteine and its oxidized dimeric form cystine are commonly believed to be synonymous in metabolic functions. Cyst(e)ine depletion not only induces amino acid response but also triggers ferroptosis, a non-apoptotic cell death. Here, we report that unlike general amino acid starvation, cyst(e)ine deprivation triggers ATF4 induction at the transcriptional level. Unexpectedly, it is the shortage of lysosomal cystine, but not the cytosolic cysteine, that elicits the adaptative ATF4 response. The lysosome-nucleus signaling pathway involves the aryl hydrocarbon receptor (AhR) that senses lysosomal cystine via the kynurenine pathway. A blockade of lysosomal cystine efflux attenuates ATF4 induction and sensitizes ferroptosis. To potentiate ferroptosis in cancer, we develop a synthetic mRNA reagent, CysRx, that converts cytosolic cysteine to lysosomal cystine. CysRx maximizes cancer cell ferroptosis and effectively suppresses tumor growth in vivo. Thus, intracellular nutrient reprogramming has the potential to induce selective ferroptosis in cancer without systematic starvation.
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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.