Evidence map›Paper›PMID 41720096›Full record

ArticleCell2026

A GPX1-OSBPL8 axis mediates noncanonical in vivo ferroptosis and cancer growth suppression.

Zhangchuan Xia, Xin Yang, Sviatlana N Samovich, Yulia Y Tyurina, Vladimir A Tyurin, Ning Kon, Jiankang Zhang, Xuejun Jiang, Brent R Stockwell, Jian Jin and 3 more

Abstract read
In one paragraph

Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

  1. Article
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  5. Article
  6. Friends, foes and signals.Nature chemical biology · 2026
    Article
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  8. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Zhangchuan XiaInstitute for Cancer Genetics and Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Xin YangInstitute for Cancer Genetics and Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Sviatlana N SamovichDepartment of Pediatrics, Division of Critical Care and Hospital Medicine, Redox Health Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA.
Yulia Y TyurinaCenter for Free Radical and Antioxidant Health and Departments of Environmental Health, Chemistry, Pharmacology and Chemical Biology, Radiation Oncology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Vladimir A TyurinCenter for Free Radical and Antioxidant Health and Departments of Environmental Health, Chemistry, Pharmacology and Chemical Biology, Radiation Oncology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Ning KonInstitute for Cancer Genetics and Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Jiankang ZhangDepartment of Physiology and Cellular Biophysics and Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA.
Xuejun JiangCell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Brent R StockwellDepartment of Chemistry, Columbia University, New York, NY 10027, USA; Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Jian JinMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences, Oncological Sciences and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Hülya BayirDepartment of Pediatrics, Division of Critical Care and Hospital Medicine, Redox Health Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA.
Valerian E KaganCenter for Free Radical and Antioxidant Health and Departments of Environmental Health, Chemistry, Pharmacology and Chemical Biology, Radiation Oncology, University of Pittsburgh, Pittsburgh, PA 15261, USA. Electronic address: kagan@pitt.edu.
Wei GuInstitute for Cancer Genetics and Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Electronic address: wg8@cumc.columbia.edu.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3M
Mutant p53 in Tumorigenesis, Invasion, and MetastasisP01CA291694 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI James J Manfredi · 2025 to 2026
$7.9M
Shared Resources Core: Ferroptosis Biomarkers and Lipidomic AnalysisP01CA291697 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Brent R. Stockwell · 2025 to 2026
$7.4M
The Organoid and Cell Culture CoreP30DK132710 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Robert F. Schwabe · 2022 to 2026
$7.2M
p53-mediated metabolic regulation in tumor suppressionR35CA253059 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Wei Gu · 2021 to 2026
$5.3M
Ferroptosis, Cellular Metabolism, and CancerR01CA204232 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI JIANG, XUEJUN · 2017 to 2025
$4.1M
Co-regulation of p53 and PD-L1 by the VPRBP-USP2 axis in transcription and ubiquitylationR01CA258390 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Wei Gu · 2022 to 2026
$2.3M
Ferroptosis and Cancer Cell SignalingR01CA258622 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Xuejun Jiang · 2022 to 2026
$2.2M
Novel small molecule USP7 Inhibitors for p53 activation and cancer therapyR01CA254970 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GU, WEI · 2021 to 2025
$1.8M
NCI NIH HHS P01 CA291694NCI NIH HHS P01 CA291697NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA013696NCI NIH HHS R01 CA204232NCI NIH HHS R01 CA254970NCI NIH HHS R01 CA258390NCI NIH HHS R01 CA258622NCI NIH HHS R35 CA253059NIDDK NIH HHS P30 DK132710
6 · The paper itself

Abstract

Ferroptosis is a tumor-suppressive mechanism with therapeutic potential. While canonical ferroptosis is usually triggered by inducers, such as erastin and RSL-3, or by glutathione peroxidase (GPX)4 loss, how ferroptosis occurs naturally in vivo without these triggers has been unclear. Building on evidence that p53 can mediate ferroptosis as a natural tumor-suppressive pathway, we describe a noncanonical, in vivo ferroptosis driven by reactive oxygen species (ROS)-induced phosphatidic acid (PA) peroxidation that proceeds without inducers. We identify GPX1 as a key regulator of this ROS-induced ferroptosis by modulating PA peroxidation. GPX1's effects depend on OSBPL8, an endoplasmic reticulum (ER)-membrane-associated oxysterol-binding protein. ROS-driven lipid peroxidation accumulates at the ER before plasma membrane rupture and cell death; GPX1 is recruited to the ER via OSBPL8 and directly reduces oxidized PA. OSBPL8 and GPX1 are overexpressed in cancers; knockdown of either promotes ROS-induced ferroptosis and suppresses tumor growth. Our data link the GPX1-OSBPL8 axis to in vivo ferroptosis and tumor suppression.

Indexed as

FerroptosisNeoplasmsPhospholipid Hydroperoxide Glutathione PeroxidaseSignal TransductionCell Line, TumorEndoplasmic ReticulumGene Knockdown TechniquesGene Knockout TechniquesHumansLipid PeroxidationOxidative StressOxysterol Binding ProteinsReactive Oxygen SpeciesGPX4 protein, humanOSBPL8 protein, humanOxysterol Binding ProteinsPhospholipid Hydroperoxide Glutathione PeroxidaseReactive Oxygen SpeciescancerferroptosisGPX1GPX4lipid peroxidationOSBPL8p53phosphatidic acidphosphatidylethanolamineROStumor suppression

Identifiers

PMID41720096
PMCPMC12927606

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Registered trials

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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.