Evidence map›Paper›PMID 41259048›Full record

ArticleProtein & cell2026

Tumor cell-specific loss of GPX4 reprograms triacylglycerol metabolism to escape ferroptosis and impair antitumor immunity in non-small cell lung cancer.

Peng Wang, Shengdan Zhang, Xin Chen, Xu-Dong Yang, Shi Huang, Huiyong Yin, Hao-Yu Duan, Fuling Zhou, Jia Yu, Bo Zhong and 1 more

Abstract read
In one paragraph

Article in Protein & cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Ferroptosis surveillance: Insights fromFerroptosis and oxidative stress · 2026
    Article
  4. Article
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

11 authors.

Peng WangDepartment of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Cancer Center, Renmin Hospital of Wuhan University, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, College of Life Sciences, State Key Laboratory of Metabolism and Regulation in Complex Organisms, State Key Laboratory of Virology and Biosafety, Hubei Provincial Research Center for Basic Biological Sciences, Wuhan University, Wuhan 430071, China.ORCID 0000-0003-3209-1368
Shengdan ZhangDepartment of Stomatology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Xin ChenAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Xu-Dong YangDepartment of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Cancer Center, Renmin Hospital of Wuhan University, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, College of Life Sciences, State Key Laboratory of Metabolism and Regulation in Complex Organisms, State Key Laboratory of Virology and Biosafety, Hubei Provincial Research Center for Basic Biological Sciences, Wuhan University, Wuhan 430071, China.
Shi HuangDepartment of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Cancer Center, Renmin Hospital of Wuhan University, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, College of Life Sciences, State Key Laboratory of Metabolism and Regulation in Complex Organisms, State Key Laboratory of Virology and Biosafety, Hubei Provincial Research Center for Basic Biological Sciences, Wuhan University, Wuhan 430071, China.
Huiyong YinAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.ORCID 0000-0001-7049-1560
Hao-Yu DuanDepartment of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Cancer Center, Renmin Hospital of Wuhan University, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, College of Life Sciences, State Key Laboratory of Metabolism and Regulation in Complex Organisms, State Key Laboratory of Virology and Biosafety, Hubei Provincial Research Center for Basic Biological Sciences, Wuhan University, Wuhan 430071, China.
Fuling ZhouResearch Center for Lifespan Health, School of Nursing, Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.ORCID 0000-0003-3745-4199
Jia YuDepartment of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Bo ZhongDepartment of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Cancer Center, Renmin Hospital of Wuhan University, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, College of Life Sciences, State Key Laboratory of Metabolism and Regulation in Complex Organisms, State Key Laboratory of Virology and Biosafety, Hubei Provincial Research Center for Basic Biological Sciences, Wuhan University, Wuhan 430071, China.ORCID 0000-0002-3832-2895
Dandan LinDepartment of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Cancer Center, Renmin Hospital of Wuhan University, Medical Research Institute, Frontier Science Center of Immunology and Metabolism, College of Life Sciences, State Key Laboratory of Metabolism and Regulation in Complex Organisms, State Key Laboratory of Virology and Biosafety, Hubei Provincial Research Center for Basic Biological Sciences, Wuhan University, Wuhan 430071, China.ORCID 0000-0003-3843-6945

Funding

Fundamental Research Funds for the Central Universities 2042022dx0003Fundamental Research Funds for the Central Universities 2042025kf0044Hubei ProvinceNational Key Research and Development Program of China 2022YFC3401500National Key Research and Development Program of China 2023YFC2306100National Key Research and Development Program of China 2024YFA1803103National Key Research and Development Program of China 2024ZD0524901Natural Science Foundation of China 32270951Natural Science Foundation of China 32470960Natural Science Foundation of China 82302072Natural Science Foundation of China 82425027Natural Science Foundation of Hubei 2025AFA026Natural Science Foundation of Wuhan 2024040701010031Postdoctoral Fellowship from the China Postdoctoral Science Foundation 2023M732708
6 · The paper itself

Abstract

Glutathione peroxidase 4 (GPX4) is a master regulator of ferroptosis, a process that has been proposed as a potential therapeutic strategy for cancer. Here, we have unexpectedly found that inducible knockout of GPX4 in tumor cells significantly promotes non-small cell lung cancer (NSCLC) progression in the autochthonous KrasLSL-G12D/+Lkb1fl/fl (KL) and KrasLSL-G12D/+Tp53fl/fl (KP) mouse models, whereas inducible overexpression of GPX4 in tumor cells exerts the opposite effect. GPX4-deficient tumor cells evade ferroptosis by upregulating the expression of DGAT1/2 to promote the synthesis of triacylglycerol (TAG) and oxidized TAG (oxTAG) and the formation of lipid droplets in cells. In addition, GPX4-deficient tumor cells secrete TAG and oxTAG into the extracellular space to induce dysfunction of antitumor CD8+ T cells, thereby coordinating an immunoinhibitory tumor microenvironment (TME). Consistently, treatment with DGAT1/2 inhibitors or inducible overexpression of GPX4 in tumor cells significantly resensitizes tumor cells to ferroptosis and ignites the activation of T cells in the TME to inhibit NSCLC progression. These findings highlight a previously uncharacterized role of tumor cell-specific GPX4 in NSCLC progression and provide potential therapeutic strategies for NSCLC.

Indexed as

Carcinoma, Non-Small-Cell LungFerroptosisLung NeoplasmsPhospholipid Hydroperoxide Glutathione PeroxidaseTriglyceridesAnimalsCell Line, TumorDiacylglycerol O-AcyltransferaseHumansMiceMice, KnockoutTumor MicroenvironmentDiacylglycerol O-Acyltransferaseglutathione peroxidase 4, mousePhospholipid Hydroperoxide Glutathione PeroxidaseTriglyceridesGPX4lipid dropletslipid releasenon-small cell lung cancertriacylglyceroltumor microenvironment

Identifiers

PMID41259048
PMCPMC13161477

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.