ArticleCell research2018
Tom20 senses iron-activated ROS signaling to promote melanoma cell pyroptosis.
Article in Cell research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 345 papers, 1 of them a synthesis that pooled it.
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Who cites it
345 citing papers in PubMed, 1 synthesis or guideline pooled it, 645 citations in OpenAlex.
- Bibliometric analysis and mini-review of global research on pyroptosis in the field of cancer.Apoptosis : an international journal on programmed cell death · 2023Pooled it
- Mitophagy in cisplatin-induced kidney injury: regulatory mechanisms and therapeutic targets.Annals of medicine · 2026Review
- Galloyl-RGD induces oxidative stress-mediated apoptosis in human melanoma cells.Molecular and cellular biochemistry · 2026Article
- PhSAN induces PANoptosis via targeting RNF25-mediated endoplasmic reticulum stress.Cell insight · 2026Article
- PTEN-L inhibits mitophagy and GSDME-dependent pyroptosis via Parkin dephosphorylation.EMBO reports · 2026Article
- Pyroptosis as a novel therapeutic target in glioblastoma multiforme: Mechanisms, molecular insights, and therapeutic potential.Molecular therapy. Nucleic acids · 2026Review
- Targeting Gasdermins for Therapeutic Interventions in Central Nervous System Injury.Neurotoxicity research · 2026Review
- The mitochondria enzyme OGDH defends against disulfidptosis by licensing METTL3-regulated NRF2 translation.Nature cell biology · 2026Article
- IFI27 and BAX are Essential for GSDME-Mediated Myeloma Cell Pyroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A Function-Centric Framework for Mitochondrial Quality Control.Biomolecules · 2026Review
- Redox signals and oxidative stress in the control of mitochondrial protein import.Protein science : a publication of the Protein Society · 2026Review
- VALD-3 Induces GSDME-Dependent Pyroptosis via ROS/JNK/Bax Pathway in Triple-Negative Breast Cancer Cells.Biochemical genetics · 2026Article
- Hypoxia-induced lnc-IRP drives oxaliplatin resistance in colorectal cancer through IRP2 sequestration and iron metabolism reprogramming.Journal of translational medicine · 2026Article
- USP9X regulates copper-induced CASP9/CASP3/GSDME-dependent pyroptosis by deubiquitinating JAK1.Apoptosis : an international journal on programmed cell death · 2026Article
- STAT3 interference-driven nanomodulators reverse lipid metabolism-associated chemoresistance and potentiate metalloimmunotherapy in breast cancer.Cell reports. Medicine · 2026Article
- CCR2 Enhances Anti-Intracellular Bacterial Infection by Modulating Macrophage Pyroptosis to Rebalance Th Immune Responses.Microorganisms · 2026Article
- Metal-dependent regulated cell death: Molecular architecture and translational frontiers.iMeta · 2026Review
- Regulated cell death programs shaping cancer therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- GSDME acts as an epigenetic modifier to promote melanoma development via centriole biogenesis regulator PLK4.Cell death and differentiation · 2026Article
- Stiripentol induces ER stress and pyroptosis in pancreatic cancer cells under metabolic stress by dysregulating SFAs/UFAs homeostasis.Cellular oncology (Dordrecht, Netherlands) · 2026Article
285 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Iron has been shown to trigger oxidative stress by elevating reactive oxygen species (ROS) and to participate in different modes of cell death, such as ferroptosis, apoptosis and necroptosis. However, whether iron-elevated ROS is also linked to pyroptosis has not been reported. Here, we demonstrate that iron-activated ROS can induce pyroptosis via a Tom20-Bax-caspase-GSDME pathway. In melanoma cells, iron enhanced ROS signaling initiated by CCCP, causing the oxidation and oligomerization of the mitochondrial outer membrane protein Tom20. Bax is recruited to mitochondria by oxidized Tom20, which facilitates cytochrome c release to cytosol to activate caspase-3, eventually triggering pyroptotic death by inducing GSDME cleavage. Therefore, ROS acts as a causative factor and Tom20 senses ROS signaling for iron-driven pyroptotic death of melanoma cells. Since iron activates ROS for GSDME-dependent pyroptosis induction and melanoma cells specifically express a high level of GSDME, iron may be a potential candidate for melanoma therapy. Based on the functional mechanism of iron shown above, we further demonstrate that iron supplementation at a dosage used in iron-deficient patients is sufficient to maximize the anti-tumor effect of clinical ROS-inducing drugs to inhibit xenograft tumor growth and metastasis of melanoma cells through GSDME-dependent pyroptosis. Moreover, no obvious side effects are observed in the normal tissues and organs of mice during the combined treatment of clinical drugs and iron. This study not only identifies iron as a sensitizer amplifying ROS signaling to drive pyroptosis, but also implicates a novel iron-based intervention strategy for melanoma therapy.
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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.