Evidence map›Paper›PMID 41215470›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

GSH as an A-A Type Allosteric Activator of PKM2: Modulating Cancer Cell Homeostasis and Ferroptosis Susceptibility.

Tsan-Jan Chen, Chi-Jen Lo, Meng-Jen Wu, Wei Yang Sit, Hsin-Yu Hsu, Yi-Cheng Huang, Chien-Hung Lu, Yu-Lun Chen, Wei-Kai Fang, Shan-Min Yang and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

18 authors.

Tsan-Jan ChenInstitute of Molecular and Cellular Biology and Department of Life Science, National Tsing Hua University, Hsinchu, 300044, Taiwan.ORCID https://orcid.org/0000-0002-9180-616X
Chi-Jen LoMetabolomics Core Laboratory, Healthy Aging Research Center, Chang Gung University, Taoyuan, 333323, Taiwan.
Meng-Jen WuInstitute of Molecular and Cellular Biology and Department of Life Science, National Tsing Hua University, Hsinchu, 300044, Taiwan.ORCID https://orcid.org/0000-0003-2303-0563
Wei Yang SitInstitute of Molecular and Cellular Biology and Department of Life Science, National Tsing Hua University, Hsinchu, 300044, Taiwan.ORCID https://orcid.org/0000-0002-9335-9172
Hsin-Yu HsuInstitute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu, 300093, Taiwan.
Yi-Cheng HuangInstitute of Molecular and Cellular Biology and Department of Life Science, National Tsing Hua University, Hsinchu, 300044, Taiwan.
Chien-Hung LuInstitute of Molecular and Cellular Biology and Department of Life Science, National Tsing Hua University, Hsinchu, 300044, Taiwan.
Yu-Lun ChenInstitute of Molecular and Cellular Biology and Department of Life Science, National Tsing Hua University, Hsinchu, 300044, Taiwan.
Wei-Kai FangInstitute of Molecular and Cellular Biology and Department of Life Science, National Tsing Hua University, Hsinchu, 300044, Taiwan.ORCID https://orcid.org/0000-0003-0498-4257
Shan-Min YangInstitute of Molecular and Cellular Biology and Department of Life Science, National Tsing Hua University, Hsinchu, 300044, Taiwan.ORCID https://orcid.org/0000-0003-0197-2621
Pei-Lien ChenInstitute of Molecular and Cellular Biology and Department of Life Science, National Tsing Hua University, Hsinchu, 300044, Taiwan.ORCID https://orcid.org/0009-0009-4417-1999
Tokuko HaraguchiGraduate School of Science, Osaka University, Toyonaka, 560-0043, Japan.
Yasushi HiraokaGraduate School of Science, Osaka University, Toyonaka, 560-0043, Japan.
Chun-Yu LinInstitute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu, 300093, Taiwan.
Mei-Ling ChengDepartment of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 333323, Taiwan.
Muh-Hwa YangInstitute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan.
Hsing-Jien KungPh.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, 110301, Taiwan.
Wen-Ching WangInstitute of Molecular and Cellular Biology and Department of Life Science, National Tsing Hua University, Hsinchu, 300044, Taiwan.ORCID https://orcid.org/0000-0002-7422-3667

Funding

Ministry of Science and Technology MOST-109-2320-B-007-008Ministry of Science and Technology MOST-109-2327-B-007-001Ministry of Science and Technology MOST-110-2320-B-007-006Ministry of Science and Technology NSTC-111-2320-B-007-001Ministry of Science and Technology NSTC-111-2320-B-007-007Ministry of Science and Technology NSTC-112-2320-B-007-001Ministry of Science and Technology NSTC-112-2320-B-007-004-MY3Ministry of Science and Technology NSTC-113-2320-B-007-001Ministry of Science and Technology NSTC-113-2321-B-037-006Ministry of Science and Technology NSTC-113-2634-F-039-001Ministry of Science and Technology NSTC-114-2320-B-007-001Ministry of Science and Technology NSTC-114-2320-B-007-008National Health Research Institutes NHRI-EX110-10917BINational Health Research Institutes NHRI-EX111-10917BINational Health Research Institutes NHRI-EX112-11211BINational Health Research Institutes NHRI-EX113-11211BINational Health Research Institutes NHRI-EX114-11211BINational Tsing Hua University and Ministry of Education's Higher Education Sprout project 109Q2705E1National Tsing Hua University and Ministry of Education's Higher Education Sprout project 110Q2705E1National Tsing Hua University and Ministry of Education's Higher Education Sprout project 111F7MDVE1National Tsing Hua University and Ministry of Education's Higher Education Sprout project 111Q2708E1National Tsing Hua University and Ministry of Education's Higher Education Sprout project 112F7MDOE1National Tsing Hua University and Ministry of Education's Higher Education Sprout project 112Q2708E1National Tsing Hua University and Ministry of Education's Higher Education Sprout project 113Q2531E1
6 · The paper itself

Abstract

This study identifies glutathione (GSH) as an endogenous A-A type allosteric activator of pyruvate kinase M2 (PKM2), stabilizing it in its active tetrameric form through binding at the A-A interface. This PKM2-GSH interaction links GSH metabolism to ferroptosis regulation. Transcriptomic analyses across cancers demonstrate strong correlations between GSH, SLC7A11, PKM2, glycolysis, and ferroptosis pathways. By depleting GSH and activating PKM2, ferroptosis is enhanced in PKM2-dependent cancer models. This approach leads to significant changes in central carbon and lipid metabolism, disrupts mitochondrial function, and drives ferroptotic cell death. The combined treatment markedly suppresses tumor growth in a xenograft model. Elevated PKM2 and SLC7A11 expression levels correlate with poorer survival outcomes, indicating their potential as biomarkers for ferroptosis-based therapy. The findings demonstrate a dual role for GSH in cellular homeostasis and identify the PKM2-GSH-SLC7A11 axis as a therapeutic target for aggressive cancers.

Indexed as

Carrier ProteinsFerroptosisGlutathioneMembrane ProteinsNeoplasmsPyruvate KinaseThyroid HormonesAllosteric RegulationAmino Acid Transport System y+AnimalsCell Line, TumorHomeostasisHumansMiceThyroid Hormone-Binding ProteinsAmino Acid Transport System y+Carrier ProteinsGlutathioneMembrane ProteinsPyruvate KinaseSLC7A11 protein, humanThyroid Hormone-Binding ProteinsThyroid Hormonescancer metabolismferroptosisglutathione (GSH)lipid metabolismpyruvate kinase M2 (PKM2)

Identifiers

PMID41215470
PMCPMC12850047

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.