ArticleOncogene2024
Hypoxia inhibits ferritinophagy-mediated ferroptosis in esophageal squamous cell carcinoma via the USP2-NCOA4 axis.
Article in Oncogene, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
What it found
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Who cites it
17 citing papers in PubMed.
- S100A9 modulates USP7-mediated stabilization of NCOA4 to promote ferroptosis in sepsis-associated acute lung injury.Redox biology · 2026Article
- Garcinoic acid promotes ferroptosis-associated growth inhibition in esophageal squamous cell carcinoma through an MDM2-associated mechanism.Translational cancer research · 2026Article
- PRRC2A-mediated mCell death & disease · 2026Article
- Deubiquitinating enzymes-mediated post-translational modifications of ferroptosis regulates cancer drug resistance.Discover oncology · 2026Review
- Translating ferroptosis into oncology: challenges, opportunities and future directions.Nature reviews. Clinical oncology · 2026Review
- Deubiquitinases at the crossroads of ferroptosis and cancer therapy: mechanisms and therapeutic potential.Molecular biology reports · 2026Review
- Multi-Omics reveals SPP1 + malignant and CXCR4Discover oncology · 2026Article
- Ferroptosis-centered strategies: redefining therapeutic resistance & adaptation in modern oncology.Apoptosis : an international journal on programmed cell death · 2026Review
- Ferroptosis in cancer toward molecular insights and clinical translation in pancreatic cancer.Molecular cancer · 2026Review
- Ferroptosis and cuproptosis in head and neck squamous cell carcinoma: interconnected mechanisms and therapeutic implications.Frontiers in pharmacology · 2026Review
- USP2-mediated PPARγ stabilization promotes hepatocellular carcinoma progression and M2 macrophage polarization via oleic acid.Journal for immunotherapy of cancer · 2025Article
- The immune microenvironment of pathogen-associated cancers and current clinical therapeutics.Molecular cancer · 2025Review
- DCAF7 recruits USP2 to facilitate hepatocellular carcinoma progression by suppressing clockophagy-induced ferroptosis.Cell death & disease · 2025Article
- Review
- Aging-associated mechanisms and metabolic vulnerabilities in esophageal carcinoma: an integrative review.Frontiers in cell and developmental biology · 2025Review
- Ferroptosis and hyperoxic lung injury: insights into pathophysiology and treatment approaches.Frontiers in pharmacology · 2025Review
- Ferroptosis-related signaling pathways in cancer drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
14 authors.
Funding
Abstract
Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy of the digestive system. Hypoxia is a crucial player in tumor ferroptosis resistance. However, the molecular mechanism of hypoxia-mediated ferroptosis resistance in ESCC remains unclear. Here, USP2 expression was decreased in ESCC cell lines subjected to hypoxia treatment and was lowly expressed in clinical ESCC specimens. Ubiquitin-specific protease 2 (USP2) depletion facilitated cell growth, which was blocked in USP2-overexpressing cells. Moreover, USP2 silencing enhanced the iron ion concentration and lipid peroxidation accumulation as well as suppressed ferroptosis, while upregulating USP2 promoted ferroptotic cell death in ESCC cells. Furthermore, knockout of USP2 in ESCC models discloses the essential role of USP2 in promoting ESCC tumorigenesis and inhibiting ferroptosis. In contrast, overexpression of USP2 contributes to antitumor effect and ferroptosis events in vivo. Specifically, USP2 stably bound to and suppressed the degradation of nuclear receptor coactivator 4 (NCOA4) by eliminating the Lys48-linked chain, which in turn triggered ferritinophagy and ferroptosis in ESCC cells. Our findings suggest that USP2 plays a crucial role in iron metabolism and ferroptosis and that the USP2/NCOA4 axis is a promising therapeutic target for the management of ESCC.
Indexed as
Identifiers
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Registered trials
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.