Evidence map›Paper›PMID 35193955›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2022

Redox signaling by glutathione peroxidase 2 links vascular modulation to metabolic plasticity of breast cancer.

Zuen Ren, Huizhi Liang, Phillip M Galbo, Malindrie Dharmaratne, Ameya S Kulkarni, Atefeh Taherian Fard, Marie Louise Aoun, Nuria Martinez-Lopez, Kimita Suyama, Outhiriaradjou Benard and 9 more

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
4.3field-weighted citation impact, top 4% of its field
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

38 citing papers in PubMed, 48 citations in OpenAlex.

  1. Review
  2. Selenium Nanoparticles Selectively Target KRAS G13D to Inhibit Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Review
  4. Selenium-Containing Compounds in Breast Cancer Therapy.Biological trace element research · 2026
    Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Glutathione-Dependent Pathways in Cancer Cells.International journal of molecular sciences · 2024
    Review
  17. Antioxidant Enzymes and Their Potential Use in Breast Cancer Treatment.International journal of molecular sciences · 2024
    Review
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 4 institutions in 2 countries.

Zuen RenDepartment of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461.ORCID 0000-0001-5951-1292
Huizhi LiangDepartment of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461.
Phillip M GalboDepartment of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461.
Malindrie DharmaratneAustralian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, 4072 QLD, Australia.ORCID 0000-0002-1694-6496
Ameya S KulkarniDepartment of Endocrinology, Albert Einstein College of Medicine, Bronx, NY 10461.ORCID 0000-0003-4495-8838
Atefeh Taherian FardAustralian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, 4072 QLD, Australia.ORCID 0000-0002-9126-4540
Marie Louise AounDepartment of Endocrinology, Albert Einstein College of Medicine, Bronx, NY 10461.ORCID 0000-0001-9216-9257
Nuria Martinez-LopezDepartment of Endocrinology, Albert Einstein College of Medicine, Bronx, NY 10461.
Kimita SuyamaDepartment of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461.
Outhiriaradjou BenardDepartment of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461.
Wei ZhengDepartment of Hematology and Medical Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Yang LiuDepartment of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461.
Joseph AlbaneseDepartment of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461.
Deyou ZhengDepartment of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461.ORCID 0000-0003-4354-5337
Jessica C MarAustralian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, 4072 QLD, Australia.
Rajat SinghDepartment of Endocrinology, Albert Einstein College of Medicine, Bronx, NY 10461.ORCID 0000-0001-9389-8574
Michael B PrystowskyDepartment of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461.ORCID 0000-0002-9548-6917
Larry NortonDepartment of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.ORCID 0000-0003-3701-9250
Rachel B HazanDepartment of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461; rachel.hazan@einsteinmed.edu.ORCID 0000-0002-1441-4584
Albert Einstein College of Medicine · USThe University of Queensland · AUIcahn School of Medicine at Mount Sinai · USMemorial Sloan Kettering Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
WORD PROCESSORP30CA013330 · NCI · YESHIVA UNIVERSITY · PI STEVEN C. ALMO · 1985 to 2026
$111.2M
The Biology of Lung Metastasis in Breast CancerP01CA257885 · NCI · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI Jonathan M. Backer · 2022 to 2026
$11.9M
NCI NIH HHS P01 CA257885NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA013330
6 · The paper itself

Abstract

In search of redox mechanisms in breast cancer, we uncovered a striking role for glutathione peroxidase 2 (GPx2) in oncogenic signaling and patient survival. GPx2 loss stimulates malignant progression due to reactive oxygen species/hypoxia inducible factor-α (HIF1α)/VEGFA (vascular endothelial growth factor A) signaling, causing poor perfusion and hypoxia, which were reversed by GPx2 reexpression or HIF1α inhibition. Ingenuity Pathway Analysis revealed a link between GPx2 loss, tumor angiogenesis, metabolic modulation, and HIF1α signaling. Single-cell RNA analysis and bioenergetic profiling revealed that GPx2 loss stimulated the Warburg effect in most tumor cell subpopulations, except for one cluster, which was capable of oxidative phosphorylation and glycolysis, as confirmed by coexpression of phosphorylated-AMPK and GLUT1. These findings underscore a unique role for redox signaling by GPx2 dysregulation in breast cancer, underlying tumor heterogeneity, leading to metabolic plasticity and malignant progression.

Indexed as

AnimalsBreast NeoplasmsCell Line, TumorCell PlasticityFemaleGlutathione PeroxidaseGlycolysisHumansHypoxia-Inducible Factor 1, alpha SubunitMetabolismMiceMice, NudeNeovascularization, PathologicOxidation-ReductionOxidative PhosphorylationReactive Oxygen SpeciesGlutathione PeroxidaseGPX2 protein, humanHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitReactive Oxygen SpeciesVascular Endothelial Growth Factor AVEGFA protein, humanbreast cancerglutathione peroxidase 2HIF1αmetabolismROS signaling

Identifiers

PMID35193955
PMCPMC8872779
OpenAlexW4213432917

What OpenQuestion 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 OpenQuestion graph.