ArticleMolecular cell2020
3D Culture Models with CRISPR Screens Reveal Hyperactive NRF2 as a Prerequisite for Spheroid Formation via Regulation of Proliferation and Ferroptosis.
Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
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Who cites it
124 citing papers in PubMed, 196 citations in OpenAlex.
- Ferroptosis in cancer: molecular mechanisms, biological roles, and therapeutic significance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Fatty acid-binding protein 5 aggravates psoriasis and psoriasis-like disease through ferroptosis.Cell death and differentiation · 2026Article
- Context-dependent synthetic lethality - an emerging precision therapeutic approach.Nature reviews. Cancer · 2026Review
- Translating ferroptosis into oncology: challenges, opportunities and future directions.Nature reviews. Clinical oncology · 2026Review
- Dose- and time-dependent cardioprotection of liproxstatin-1 via sequential modulation of ferroptosis pathways after myocardial ischemia-reperfusion.Molecular and cellular biochemistry · 2026Article
- Physiologically relevant 3D CRISPR screening enhances mechanistic insight into chemical toxicity compared to 2D screening.Toxicology · 2026Article
- A Covalent Allosteric Molecular Glue Suppresses NRF2-Dependent Cancer Growth.Cancer discovery · 2026Article
- Baicalein Attenuated Recurrent Pregnancy Loss by Inhibiting Ferroptosis via Activation of Nrf2/GPx4 Axis.Chinese journal of integrative medicine · 2026Article
- Mendelian Randomization and ScTranscriptomics Reveal a Lipid Low Malignant Cells Driving Immunosuppression and Matrix Remodeling in Oral squamous cell carcinoma.International dental journal · 2026Article
- Organelle-specific regulation of ferroptosis.Biology direct · 2026Review
- Article
- Ironing out COPD: ferroptosis-driven immune dysregulation, metabolic rewiring, and precision therapeutic opportunities.Frontiers in immunology · 2026Review
- Huang-qin decoction increases the sensitivity of EGFR-TKIs to NSCLC cells by regulating stat3/GPX4 to induce redox ratio and ROS to inhibit CSCs.Journal of traditional and complementary medicine · 2026Article
- Targeting FSP1 triggers ferroptosis in lung cancer.Nature · 2026Article
- Physiologically Relevant 3D CRISPR Screening Enhances Mechanistic Insight into Chemical Toxicity Compared to 2D Screening.bioRxiv : the preprint server for biology · 2025Article
- Unraveling Oxidative Threads: Stress, Pathology, and Resilience in Biochemistry, Molecular, and Cellular Biology (2023-2025).Current issues in molecular biology · 2025Article
- Activating NRF2Cancer gene therapy · 2025Article
- Lipid Composition Alters Ferroptosis Sensitivity.Cancer research · 2025Article
- Dimethyl fumarate alleviates inflammation during high altitude hypoxia induced acute lung injury by upregulating Nrf2/SLC7A11 pathway in ferroptosis.Clinical proteomics · 2025Article
- Differential cell survival outcomes in response to diverse amino acid stress.Life science alliance · 2025Article
64 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
Abstract
Cancer-associated mutations that stabilize NRF2, an oxidant defense transcription factor, are predicted to promote tumor development. Here, utilizing 3D cancer spheroid models coupled with CRISPR-Cas9 screens, we investigate the molecular pathogenesis mediated by NRF2 hyperactivation. NRF2 hyperactivation was necessary for proliferation and survival in lung tumor spheroids. Antioxidant treatment rescued survival but not proliferation, suggesting the presence of distinct mechanisms. CRISPR screens revealed that spheroids are differentially dependent on the mammalian target of rapamycin (mTOR) for proliferation and the lipid peroxidase GPX4 for protection from ferroptosis of inner, matrix-deprived cells. Ferroptosis inhibitors blocked death from NRF2 downregulation, demonstrating a critical role of NRF2 in protecting matrix-deprived cells from ferroptosis. Interestingly, proteomics analyses show global enrichment of selenoproteins, including GPX4, by NRF2 downregulation, and targeting NRF2 and GPX4 killed spheroids overall. These results illustrate the value of spheroid culture in revealing environmental or spatial differential dependencies on NRF2 and reveal exploitable vulnerabilities of NRF2-hyperactivated tumors.
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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.