ArticleCell death & disease2024
Phosphatase LHPP confers prostate cancer ferroptosis activation by modulating the AKT-SKP2-ACSL4 pathway.
Article in Cell death & disease, 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.
- Ferroptosis and prostate cancer: A translational path from molecular mechanisms to precision therapy.Genes & diseases · 2026Review
- Chondrosarcoma: A comprehensive review of tumor biology, clinical behavior, and therapeutic advances.Cancer treatment reviews · 2026Review
- ACSL4 in Alzheimer's disease: Pathogenetic mechanisms and potential therapeutic targets.Genes & diseases · 2026Review
- The multifaceted roles of the ACSL family in cancer: Metabolic reprogramming, ferroptosis regulation and tumour immune microenvironment remodelling.Clinical and translational medicine · 2026Review
- Integrated regulation of ferroptosis in prostate cancer covering mechanisms, resistance, and translational opportunities.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Acyl-CoA Synthetase Long-Chain Family Member 4 in Liver Injury: Multidimensional Regulation and Therapeutic Potential.Gastroenterology research · 2026Review
- Post-translational modifications in ferroptosis: mechanisms and therapeutic potential.International journal of biological sciences · 2026Review
- Characterization of Differential GPX4 Essentiality Between Intrahepatic and Extrahepatic Cholangiocarcinoma via Leveraging of a Large-Scale Functional Genomic Screen.International journal of molecular sciences · 2025Article
- Glucocorticoid-mediated suppression of the CCL2-CCR2 axis drives monocyte dysfunction in severe pneumonia among immunocompromised hosts.Respiratory research · 2025Article
- EMX2OS serves as a biomarker of neonatal sepsis and participates acute lung injury through enhancing ferroptosis.Frontiers in pediatrics · 2025Article
- Ferroptosis-Related Transcriptional Level Changes and the Role of CIRBP in Glioblastoma Cells Ferroptosis.Biomedicines · 2024Article
- SKP2 E3 ligase in urological malignancies: a critical regulator of the cell cycle and therapeutic target.Cell cycle (Georgetown, Tex.)Review
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Authors and funding
14 authors.
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Abstract
LHPP, a novel, recognized tumor suppressor, exerts a critical influence on the regulation of tumor cell proliferation and survival by modulating various signaling pathways with its phosphatase activity. Here, we unveil a robust correlation between reduced LHPP expression and adverse prognosis in prostate cancer. We demonstrate that LHPP interacts with AKT, thereby dampening AKT phosphorylation and subsequently inhibiting ACSL4 phosphorylation at the T624 site. This interaction impedes phosphorylation-dependent ubiquitination, thwarting SKP2 from recognizing and binding to ACSL4 at the K621 site. As a result, ACSL4 is spared from lysosomal degradation, leading to its accumulation and the promotion of lipid peroxidation, and ferroptosis. Moreover, our findings reveal that Panobinostat, a potent histone-deacetylase inhibitor, intricately regulates LHPP expression at multiple levels through the inhibition of HDAC3. This complex modulation enhances the ferroptosis pathway, offering a novel mechanism for curtailing the growth of prostate tumors and highlighting its significant translational potential for clinical application.
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