Evidence map›Paper›PMID 41013471›Full record

ArticleBreast cancer research : BCR2025

Glutamine synthetase shields triple-negative breast cancer cells from ferroptosis in metastasis triggered by glutamine deprivation.

Zhaoting Yang, Xinyu Lian, Yuan Luo, Qiao Ye, Guangjin Guo, Guoquan Liu

Abstract read
In one paragraph

Article in Breast cancer research : BCR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

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4 · The record

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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

6 authors.

Zhaoting Yang *Laboratory of Clinical Medicine, Air Force Medical Center, PLA, Air Force Medical University, Fu Cheng Rd. 28, Beijing, 100142, China.
Xinyu Lian *State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. 38, Beijing, 100191, China.
Yuan LuoLaboratory of Clinical Medicine, Air Force Medical Center, PLA, Air Force Medical University, Fu Cheng Rd. 28, Beijing, 100142, China.
Qiao YeLaboratory of Clinical Medicine, Air Force Medical Center, PLA, Air Force Medical University, Fu Cheng Rd. 28, Beijing, 100142, China.
Guangjin GuoLaboratory of Clinical Medicine, Air Force Medical Center, PLA, Air Force Medical University, Fu Cheng Rd. 28, Beijing, 100142, China.
Guoquan LiuState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. 38, Beijing, 100191, China. guoquanliu@bjmu.edu.cn.

Funding

National Natural Science Foundation of China 82203788, 91643112
6 · The paper itself

Abstract

backgroundEpithelial-mesenchymal transition (EMT) in cancer cell metastasis involves complicated metabolic plasticity to survive the highly challenging environment, such as oxidative stress, after subsequent circulation in the bloodstream. Glutamine synthetase (GS) is an enzyme that converts glutamate and ammonia to glutamine (Gln) during Gln deprivation stress. This study revealed for the first time that GS plays an important role in protecting triple-negative breast cancer (TNBC) cells from ferroptosis during Gln deprivation-induced EMT, namely ferroptosis-resistant EMT (FR-EMT).

methodsTo better understand this finding, we focused on the mechanism of GS-mediated FR-EMT in TNBC through transcriptomic analysis and murine metastasis modeling.

resultsThis study specifically investigated the effects of GS on lipid peroxidation and iron metabolism, the two major metabolic disorders in ferroptosis. An abnormal increase in monounsaturated fatty acids (MUFAs) mediated by mechanistic target of rapamycin complex 1 (mTORC1) decreased the ferroptosis sensitivity under Gln deprivation. Additionally, aberrant iron metabolism via lipocalin 2 (LCN2) and transferrin receptor (TFRC) affected the sensitivity to ferroptosis. Moreover, this study confirmed that GS protects TNBC cells from ferroptosis and increases their ability to survive during subsequent metastasis through the blood in the lung metastasis mouse model.

conclusionThis investigation provides insights into the role of ferroptosis in metastasis and demonstrates that GS may be a viable target for preventing metastases in TNBC.

Indexed as

Epithelial-Mesenchymal TransitionFerroptosisGlutamate-Ammonia LigaseGlutamineTriple Negative Breast NeoplasmsAnimalsCell Line, TumorFatty Acids, MonounsaturatedFemaleGene Expression ProfilingHumansIronLipid PeroxidationLipocalin-2Lung NeoplasmsMechanistic Target of Rapamycin Complex 1Fatty Acids, MonounsaturatedGlutamate-Ammonia LigaseGlutamineIronLipocalin-2Mechanistic Target of Rapamycin Complex 1Epithelial-mesenchymal transitionFerroptosisGlutamineGlutamine synthetaseTriple-negative breast cancer

Identifiers

PMID41013471
PMCPMC12465765

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.