ArticleCommunications biology2024
Tumor suppressor Par-4 activates autophagy-dependent ferroptosis.
Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it.
- [Research Advances on the Autophagy and Ferroptosis in the Development and Treatment of Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Pooled it
- Par-4/TERT induced autophagy dysregulation in regulating glycolysis in hyperglycemia combined with hepatocellular carcinoma.Journal of bioenergetics and biomembranes · 2026Article
- PAWR augments anti-RNA viral innate immunity by promoting the PIM2-XBP1s-RIG-I signaling axis.Nature communications · 2026Article
- The dual role of the crosstalk between autophagy and ferroptosis in lung cancer treatment: Advances in mechanisms and therapeutic strategies (Review).International journal of molecular medicine · 2026Review
- Targeting dormant cancer cells: ferroptosis as a precision therapeutic strategy.Cellular & molecular biology letters · 2026Review
- Proteomic landscape analysis of undifferentiated pleomorphic sarcoma.Genome medicine · 2026Article
- Autophagy-Ferroptosis Interplay Network: Redefining Therapeutic Paradigms for Diabetic Wound Healing.Journal of inflammation research · 2026Review
- Remodeling the tumor immune microenvironment: mechanisms of crosstalk between regulated cell death macrophages.Frontiers in immunology · 2026Review
- DGEAR: a web-based application for differential gene expression analysis and downstream functional insights.Functional & integrative genomics · 2025Article
- Selective autophagy in hepatocellular carcinoma: Mechanisms, roles and therapeutic implications (Review).Experimental and therapeutic medicine · 2025Review
- Crosstalk between ferroptosis and autophagy: broaden horizons of cancer therapy.Journal of translational medicine · 2025Review
- Unlocking ferroptosis to overcome cancer stem cells-mediated treatment failure and immune evasion.Frontiers in immunology · 2025Review
- Mechanism of ferroptosis resistance in cancer cells.Cancer drug resistance (Alhambra, Calif.) · 2024Review
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ferroptosis is a unique iron-dependent form of non-apoptotic cell death characterized by devastating lipid peroxidation. Whilst growing evidence suggests that ferroptosis is a type of autophagy-dependent cell death, the underlying molecular mechanisms regulating ferroptosis are largely unknown. In this study, through an unbiased RNA-sequencing screening, we demonstrate the activation of a multi-faceted tumor-suppressor protein Par-4/PAWR during ferroptosis. Functional studies reveal that genetic depletion of Par-4 effectively blocks ferroptosis, whereas Par-4 overexpression sensitizes cells to undergo ferroptosis. More importantly, we have determined that Par-4-triggered ferroptosis is mechanistically driven by the autophagic machinery. Upregulation of Par-4 promotes activation of ferritinophagy (autophagic degradation of ferritin) via the nuclear receptor co-activator 4 (NCOA4), resulting in excessive release of free labile iron and, hence, enhanced lipid peroxidation and ferroptosis. Inhibition of Par-4 dramatically suppresses the NCOA4-mediated ferritinophagy signaling axis. Our results also establish that Par-4 activation positively correlates with reactive oxygen species (ROS) production, which is critical for ferritinophagy-mediated ferroptosis. Furthermore, Par-4 knockdown effectively blocked ferroptosis-mediated tumor suppression in the mouse xenograft models. Collectively, these findings reveal that Par-4 has a crucial role in ferroptosis, which could be further exploited for cancer therapy.
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