ArticleNature communications2019
A GPX4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 545 papers.
What it found
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Who cites it
545 citing papers in PubMed, 846 citations in OpenAlex.
- Targeted extracellular degradation of LRP8 promotes ferroptosis in cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- SOX4 Knockdown Represses Pancreatic Acinar Cells Ferroptosis in Acute Pancreatitis Through Reducing LPCAT3 Expression.Digestive diseases and sciences · 2026Article
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Bilirubin and the Yellow Players in Ferroptosis: A Delicate Balance in Human Health and Disease, with a Focus on the Liver, Cardiovascular System, and Brain.Biomolecules · 2026Review
- Ferroptosis in kidney disease.Nature reviews. Nephrology · 2026Review
- Renal cell carcinoma: molecular understanding and therapeutic development.Cell death and differentiation · 2026Review
- Single-Cell Transcriptomic Analysis Reveals Ferroptosis-Related Signatures and Tumor Microenvironment Heterogeneity in Epithelial Ovarian Cancer.Cancer medicine · 2026Article
- Ferroptosis in skeletal muscle: from molecular mechanisms to therapeutic interventions.Journal of orthopaedic translation · 2026Review
- Regulation of lipid oxidation and ferroptosis by a tunable axis of vitamin E, high-density lipoprotein, and scavenger receptor class B type 1.The Journal of biological chemistry · 2026Article
- Silencing arachidonate 15-lipoxygenase alleviates hypoxia-induced cognitive impairment through the mediation of phospholipase A2 group IVC-LPC18:0 to suppress ferroptosis.Molecular biomedicine · 2026Article
- Article
- Review
- Emerging tools to investigate the contribution of selenium to ferroptosis and beyond.Nature chemical biology · 2026Review
- HIFs: The central drivers of tumors and their role as molecular switches in targeted therapy?Acta pharmaceutica Sinica. B · 2026Review
- Molecular mechanisms of iron metabolism and ferroptosis in cardiovascular diseases and intervention strategies targeting natural products (Review).Molecular medicine reports · 2026Review
- Opposing roles of DGAT-mediated lipid droplet biogenesis in the regulation of ferroptosis sensitivity.The FEBS journal · 2026Article
- Double-bond geometry determines fatty acid metabolic fate and ferroptosis sensitivity.bioRxiv : the preprint server for biology · 2026Article
- GPX4 in the Tumor Microenvironment: Not Just Inhibiting Ferroptosis, but Immuno-Metabolic Regulation.Biomolecules · 2026Review
- Regulated cell death plasticity in cancer: thresholds, reversibility, and therapeutic failure.Journal of translational medicine · 2026Review
- Osalmid inhibits lung adenocarcinoma progression and enhances EGFR-TKI responses: a preclinical and translational study.Translational lung cancer research · 2026Article
485 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 2 institutions in 1 country.
Funding
Abstract
Clear-cell carcinomas (CCCs) are a histological group of highly aggressive malignancies commonly originating in the kidney and ovary. CCCs are distinguished by aberrant lipid and glycogen accumulation and are refractory to a broad range of anti-cancer therapies. Here we identify an intrinsic vulnerability to ferroptosis associated with the unique metabolic state in CCCs. This vulnerability transcends lineage and genetic landscape, and can be exploited by inhibiting glutathione peroxidase 4 (GPX4) with small-molecules. Using CRISPR screening and lipidomic profiling, we identify the hypoxia-inducible factor (HIF) pathway as a driver of this vulnerability. In renal CCCs, HIF-2α selectively enriches polyunsaturated lipids, the rate-limiting substrates for lipid peroxidation, by activating the expression of hypoxia-inducible, lipid droplet-associated protein (HILPDA). Our study suggests targeting GPX4 as a therapeutic opportunity in CCCs, and highlights that therapeutic approaches can be identified on the basis of cell states manifested by morphological and metabolic features in hard-to-treat cancers.
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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.