ArticleJournal of cancer research and clinical oncology2024
Abrogating PDK4 activates autophagy-dependent ferroptosis in breast cancer via ASK1/JNK pathway.
Article in Journal of cancer research and clinical oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 10 citations in OpenAlex.
- Review
- Article
- Dual activation of cuproptosis and excessive autophagy by copper-bismuth metal-organic frameworks-loaded detachable microneedles in oral leukoplakia.Materials today. Bio · 2026Article
- PRDX1 depletion predisposes to ferroptosis through inhibiting the cAMP pathway in B-cell acute lymphoblastic leukemia.Cancer gene therapy · 2026Article
- PDK4 acts via hippo signaling to inhibit ferroptosis and reduce gemcitabine sensitivity in pancreatic cancer.Journal of molecular histology · 2026Article
- Multi-dimensional analysis reveals the potential of PDK4 as a tumor biomarker and target for immunotherapy.Discover oncology · 2026Article
- Identification of mitochondrial associated genes as diagnostic biomarkers for basal cell carcinoma: Comprehensive bioinformatics analysis and experimental validation.Glycoconjugate journal · 2026Article
- Interactions between LncRNAs and MAPK signaling pathways in the pathogenesis of breast cancer.Cancer cell international · 2025Review
- Targeting ASK1 signaling in neurodegeneration: molecular insights and therapeutic promise.Apoptosis : an international journal on programmed cell death · 2025Review
- Myocardial pyruvate dehydrogenase kinase 4 drives sex-specific cardiac responses to endotoxemia.JCI insight · 2025Article
- Mitochondria at the Heart of Sepsis: Mechanisms, Metabolism, and Sex Differences.International journal of molecular sciences · 2025Review
- Targeting ferroptosis reveals a new strategy for breast cancer treatment: a bibliometric study.Discover oncology · 2024Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundTargeting ferroptosis mediated by autophagy presents a novel therapeutic approach to breast cancer, a mortal neoplasm on the global scale. Pyruvate dehydrogenase kinase isozyme 4 (PDK4) has been denoted as a determinant of breast cancer metabolism. The target of this study was to untangle the functional mechanism of PDK4 in ferroptosis dependent on autophagy in breast cancer.
methodsRT-qPCR and western blotting examined PDK4 mRNA and protein levels in breast cancer cells. Immunofluorescence staining appraised light chain 3 (LC3) expression. Fe (2 +) assay estimated total iron level. Relevant assay kits and C11-BODIPY (591/581) staining evaluated lipid peroxidation level. DCFH-DA staining assayed intracellular reactive oxygen species (ROS) content. Western blotting analyzed the protein levels of autophagy, ferroptosis and apoptosis-signal-regulating kinase 1 (ASK1)/c-Jun N-terminal kinase (JNK) pathway-associated proteins.
resultsPDK4 was highly expressed in breast cancer cells. Knockdown of PDK4 induced the autophagy of breast cancer cells and 3-methyladenine (3-MA), an autophagy inhibitor, countervailed the promoting role of PDK4 interference in ferroptosis in breast cancer cells. Furthermore, PDK4 knockdown activated ASK1/JNK pathway and ASK1 inhibitor (GS-4997) partially abrogated the impacts of PDK4 absence on the autophagy and ferroptosis in breast cancer cells.
conclusionTo sum up, deficiency of PDK4 activated ASK1/JNK pathway to stimulate autophagy-dependent ferroptosis in breast cancer.
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