ArticleNeoplasia (New York, N.Y.)2010
Absence of glutathione peroxidase 4 affects tumor angiogenesis through increased 12/15-lipoxygenase activity.
Article in Neoplasia (New York, N.Y.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 81 citations in OpenAlex.
- 15-LOX-catalytic bias towards ether-(alkenyl)-ETE-PEs oxidation bestows selectivity of PRO-ferroptotic cell death signaling.Nature communications · 2026Article
- A feedback loop between cell proliferation and ROS regulates ferroptosis sensitivity.Frontiers in cell and developmental biology · 2026Article
- Glutathione Peroxidases: An Emerging and Promising Therapeutic Target for Pancreatic Cancer Treatment.Antioxidants (Basel, Switzerland) · 2024Review
- Emerging role of ferroptosis in metabolic dysfunction-associated steatotic liver disease: revisiting hepatic lipid peroxidation.EBioMedicine · 2024Review
- The mechanism of ferroptosis and its related diseases.Molecular biomedicine · 2023Review
- Curdione induces ferroptosis mediated by m6A methylation via METTL14 and YTHDF2 in colorectal cancer.Chinese medicine · 2023Article
- Hepatic COX1 loss leads to impaired autophagic flux and exacerbates nonalcoholic steatohepatitis.Acta pharmaceutica Sinica. B · 2023Article
- Lipid Mediators Metabolic Chaos of Asthmatic Mice Reversed by Rosmarinic Acid.Molecules (Basel, Switzerland) · 2023Article
- Prospects for Anti-Tumor Mechanism and Potential Clinical Application Based on Glutathione Peroxidase 4 Mediated Ferroptosis.International journal of molecular sciences · 2023Review
- Male infertility and somatic health - insights into lipid damage as a mechanistic link.Nature reviews. Urology · 2022Review
- ISCA2 inhibition decreases HIF and induces ferroptosis in clear cell renal carcinoma.Oncogene · 2022Article
- Extracellular vesicles in β cell biology: Role of lipids in vesicle biogenesis, cargo, and intercellular signaling.Molecular metabolism · 2022Review
- Ferroptosis Involvement in Glioblastoma Treatment.Medicina (Kaunas, Lithuania) · 2022Review
- Ferroptosis: A potential opportunity for intervention of pre-metastatic niche.Frontiers in oncology · 2022Review
- The Molecular Mechanisms of Ferroptosis and Its Role in Blood-Brain Barrier Dysfunction.Frontiers in cellular neuroscience · 2022Review
- Emerging mechanisms and targeted therapy of ferroptosis in cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Ferroptosis: mechanisms, biology and role in disease.Nature reviews. Molecular cell biology · 2021Review
- Ferroptosis: A Trigger of Proinflammatory State Progression to Immunogenicity in Necroinflammatory Disease.Frontiers in immunology · 2021Review
- Targeting Lipid Peroxidation for Cancer Treatment.Molecules (Basel, Switzerland) · 2020Review
- Together we stand, apart we fall: how cell-to-cell contact/interplay provides resistance to ferroptosis.Cell death & disease · 2020Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The selenoenzyme glutathione peroxidase 4 (GPx4) has been described to control specific cyclooxygenases (COXs) and lipoxygenases (LOXs) that exert substantiated functions in tumor growth and angiogenesis. Therefore, we hypothesized a putative regulatory role of GPx4 during tumor progression and created transformed murine embryonic fibroblasts with inducible disruption of GPx4. GPx4 inactivation caused rapid cell death in vitro, which could be prevented either by lipophilic antioxidants or by 12/15-LOX-specific inhibitors, but not by inhibitors targeting other LOX isoforms or COX. Surprisingly, transformed GPx4(+/-) cells did not die when grown in Matrigel but gave rise to tumor spheroids. Subcutaneous implantation of tumor cells into mice resulted in knockout tumors that were indistinguishable in volume and mass in comparison to wild-type tumors. However, further analysis revealed a strong vascular phenotype. We observed an increase in microvessel density as well as a reduction in the number of large diameter vessels covered by smooth muscle cells. This phenotype could be linked to increased 12/15-LOX activity that was accompanied by an up-regulation of basic fibroblast growth factor and down-regulation of vascular endothelial growth factor A protein expression. Indeed, pharmacological inhibition of 12/15-LOX successfully reversed the tumor phenotype and led to "normalized" vessel morphology. Thus, we conclude that GPx4, through controlling 12/15-LOX activity, is an important regulator of tumor angiogenesis as well as vessel maturation.
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