ArticleNature2007
RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels.
Article in Nature, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 914 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
914 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,597 citations in OpenAlex.
- Ferroptosis as a Translational Axis in Small Cell Lung Cancer: A Systematic Review of Redox Pathways and Precision Oncology Prospects.Oncology research · 2026Pooled it
- Pharmacological mechanisms of traditional Chinese medicine in treating gastric cancer: a focus on the ferroptosis regulation.Frontiers in pharmacology · 2025Pooled it
- Targeting ferroptosis in cancer: molecular mechanisms and emerging therapeutic strategies.Biochemistry and biophysics reports · 2026Review
- Respiratory viruses induce ferroptosis-like features in lung epithelial cells.Microbiology spectrum · 2026Article
- SMCO2 inhibits ferroptosis through the VDAC1-STAT3 axis by modulating MAM homeostasis in ovarian cancer.Oncogene · 2026Article
- 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
- The impact of fusaric acid on oxidative stress, ferritinophagy, and ferroptosis pathways: a review.Archives of toxicology · 2026Review
- Harnessing copper-iron crosstalk: A novel strategy to combat hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2026Review
- Ferroptosis in depression: mechanisms, association, and therapeutic strategies.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Role of voltage-dependent anion channel 1 in neurodegeneration: Mechanisms, implications, and therapeutic potential.Neural regeneration research · 2026Article
- Erastin-sensitive VDAC2 contributes to time-course peritoneal fibrosis via ferroptosis signaling induction.Molecular and cellular biochemistry · 2026Article
- Ferroptosis: Newly Emerged Regulator for Human Disease.MedComm · 2026Review
- Article
- Selective autophagy in kidney health and disease.Nature reviews. Nephrology · 2026Review
- Molecular mechanisms of iron metabolism and ferroptosis in cardiovascular diseases and intervention strategies targeting natural products (Review).Molecular medicine reports · 2026Review
- Concurrent Stereotactic Body Radiation Therapy and KRAS Inhibition Synergistically Improve Pre-clinical Pancreatic Cancer Treatment.bioRxiv : the preprint server for biology · 2026Article
- Review
- APOE4 Drives Uniquely Dysfunctional Human Microglial States in Alzheimer's Disease.bioRxiv : the preprint server for biology · 2026Article
- Current research on the role of HIF in intervertebral disc degeneration.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Review
- Crosstalk between autophagy and ferroptosis in liver diseases (Review).International journal of molecular medicine · 2026Review
854 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
14 authors at 3 institutions in 1 country.
Funding
Abstract
Therapeutics that discriminate between the genetic makeup of normal cells and tumour cells are valuable for treating and understanding cancer. Small molecules with oncogene-selective lethality may reveal novel functions of oncoproteins and enable the creation of more selective drugs. Here we describe the mechanism of action of the selective anti-tumour agent erastin, involving the RAS-RAF-MEK signalling pathway functioning in cell proliferation, differentiation and survival. Erastin exhibits greater lethality in human tumour cells harbouring mutations in the oncogenes HRAS, KRAS or BRAF. Using affinity purification and mass spectrometry, we discovered that erastin acts through mitochondrial voltage-dependent anion channels (VDACs)--a novel target for anti-cancer drugs. We show that erastin treatment of cells harbouring oncogenic RAS causes the appearance of oxidative species and subsequent death through an oxidative, non-apoptotic mechanism. RNA-interference-mediated knockdown of VDAC2 or VDAC3 caused resistance to erastin, implicating these two VDAC isoforms in the mechanism of action of erastin. Moreover, using purified mitochondria expressing a single VDAC isoform, we found that erastin alters the permeability of the outer mitochondrial membrane. Finally, using a radiolabelled analogue and a filter-binding assay, we show that erastin binds directly to VDAC2. These results demonstrate that ligands to VDAC proteins can induce non-apoptotic cell death selectively in some tumour cells harbouring activating mutations in the RAS-RAF-MEK pathway.
Indexed as
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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.