ArticleMedComm2023
ATR-dependent ubiquitin-specific protease 20 phosphorylation confers oxaliplatin and ferroptosis resistance.
Article in MedComm, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 28 citations in OpenAlex.
- The role of ubiquitin system in ageing-related diseases and potential therapeutic opportunities.Molecular biomedicine · 2026Review
- Deubiquitinating enzymes-mediated post-translational modifications of ferroptosis regulates cancer drug resistance.Discover oncology · 2026Review
- Quantitative susceptibility mapping reveals abnormal iron reduction in deep gray matter of children with global developmental delay.Pediatric radiology · 2026Article
- USP20 governs tyrosine kinase inhibitors resistance through ferroptosis evasion by targeting GPX4 in cancers.Redox biology · 2026Article
- Targeting ATR and PI3Kα Pathways Promotes Ferroptosis inCancers · 2026Article
- A20 Facilitates Oxaliplatin Sensitivity in Colorectal Cancer Through Monoubiquitylation of IKK-β.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Post-translational modifications in ferroptosis: mechanisms and therapeutic potential.International journal of biological sciences · 2026Review
- Cardiomyocyte-derived USP20 mitigates myocardial ischemia/reperfusion injury through deubiquitinating GRP78.Theranostics · 2026Article
- USP20, a Super-enhancer Regulated Gene, Promotes Acute Myeloid Leukemia Progression through CTNNB1 Deubiquitination.International journal of biological sciences · 2026Article
- BE screen reveals METTL3 S2 dephosphorylation sensitizes gastric cancer cells to oxaliplatin by interfering METTL3-eIF3H interaction.Science advances · 2025Article
- O-GlcNAcylation of SPOP regulates colorectal cancer progression and ferroptosis by mediating β-catenin degradation.Cell death discovery · 2025Article
- USP2-mediated PPARγ stabilization promotes hepatocellular carcinoma progression and M2 macrophage polarization via oleic acid.Journal for immunotherapy of cancer · 2025Article
- Cardiomyocyte USP20 alleviates septic cardiomyopathy by deubiquitinating and inhibiting NLRP3 activity.Clinical and translational medicine · 2025Article
- YY1-induced USP43 drives ferroptosis suppression by FASN stabilization and subsequent activation of SLC7A11 in ovarian cancer.Cell death & disease · 2025Article
- Review
- Deubiquitinating enzymes: Key regulators of ferroptosis and pyroptosis and novel targets for cancer intervention.International journal of biological sciences · 2025Review
- Research progress of ferroptosis pathway and its related molecular ubiquitination modification in liver cancer.Frontiers in oncology · 2025Review
- Mechanism of Ferroptosis and Its Role in Disease Development.International journal of biological sciences · 2025Review
- Pan-cancer analysis reveals MTTP as a prognostic and immunotherapeutic biomarker in human tumors.Frontiers in immunology · 2025Article
- Deubiquitylating Enzymes in Hepatocellular Carcinoma.International journal of biological sciences · 2025Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxaliplatin (OXA) resistance is a major clinic challenge in hepatocellular carcinoma (HCC). Ferroptosis is a kind of iron-dependent cell death. Triggering ferroptosis is considered to restore sensitivity to chemotherapy. In the present study, we found that USP20 was overexpressed in OXA-resistant HCC cells. High expression of USP20 in HCC was associated with poor prognosis. USP20 contributes OXA resistance and suppress ferroptosis in HCC. Pharmacological inhibition or knockdown of USP20 triggered ferroptosis and increased the sensitivity of HCC cells to OXA both in vitro and in vivo. Coimmunoprecipitation results revealed that the UCH domain of USP20 interacted with the N terminal of SLC7A11. USP20 stabilized SLC7A11 via removing K48-linked polyubiquitination of SLC7A11 protein at K30 and K37. Most importantly, DNA damage-induced ATR activation was required for Ser132 and Ser368 phosphorylation of USP20. USP20 phosphorylation at Ser132 and Ser368 enhanced its stability and thus conferred OXA and ferroptosis resistance of HCC cells. Our study reveals a previously undiscovered association between OXA and ferroptosis and provides new insight into mechanisms regarding how DNA damage therapies always lead to therapeutic resistance. Therefore, targeting USP20 may mitigate the development of drug resistance and promote ferroptosis of HCC in patients receiving chemotherapy.
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