ArticleCell death and differentiation2020
The deubiquitylase USP2 maintains ErbB2 abundance via counteracting endocytic degradation and represents a therapeutic target in ErbB2-positive breast cancer.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 55 citations in OpenAlex.
- Therapeutic Potential of Targeting USP2 in Pediatric Group 3 and 4 Medulloblastomas: Insights from In Silico, Ex Vivo, and In Vitro Studies.Cerebellum (London, England) · 2026Article
- Article
- Identification of telomere-related genes in the progression of colon adenocarcinoma: a bioinformatics analysis.Journal of gastrointestinal oncology · 2026Article
- USP2 is an androgen-repressed survival factor that stabilises oncoproteins to facilitate therapy resistance in prostate cancer.Cell death & disease · 2026Article
- Endothelial USP2a-METTL16 loop potentiates IL-6 signaling via mCell death and differentiation · 2026Article
- Ubiquitin-Specific Protease 2 (USP2) as a Modulator of Energy Metabolism: A Review of Studies Using Animal and Cellular Models.Biomedicines · 2026Review
- Proximity proteomics reveals OTUD6B regulation of stress granule dynamics through coalescence with VCP/p97.Cell death & disease · 2026Article
- Pyrotinib inhibits the tumorigenicity of HER2-positive non-small cell lung cancer by inducing ARIH1/ubiquitin/lysosome-dependent degradation of HER2.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Research progress of DUB enzyme in breast cancer.Clinical and experimental medicine · 2025Review
- DCAF7 recruits USP2 to facilitate hepatocellular carcinoma progression by suppressing clockophagy-induced ferroptosis.Cell death & disease · 2025Article
- Targeting USP2 induces degradation of PML-RARα with or without drug-resistant mutations in acute promyelocytic leukemia.Acta biochimica et biophysica Sinica · 2025Article
- Periplocin potentiates ferroptotic cell death in non-small cell lung cancer by inducing the degradation of Nrf2.Cancer cell international · 2025Article
- USP39 promote post-translational modifiers to stimulate the progress of cancer.Discover oncology · 2025Review
- Dauricine Impedes the Tumorigenesis of Lung Adenocarcinoma by Regulating Nrf2 and Reactive Oxygen Species.Cells · 2025Article
- Oncogenic RIT1 mutations confer ferroptosis vulnerability in lung adenocarcinoma.Biology direct · 2025Article
- USP39 phase separates into the nucleolus and drives lung adenocarcinoma progression by promoting GLI1 expression.Cell communication and signaling : CCS · 2025Article
- Mechanisms of resistance to antibody-drug conjugates in cancer therapy: molecular basis and therapeutic strategies.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Identification of USP2 as a novel target to induce degradation of KRAS in myeloma cells.Acta pharmaceutica Sinica. B · 2024Article
- Roles of posttranslational modifications in lipid metabolism and cancer progression.Biomarker research · 2024Review
- The role of deubiquitinase USP2 in driving bladder cancer progression by stabilizing EZH2 to epigenetically silence SOX1 expression.Translational oncology · 2024Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ErbB2 overexpression identifies a subclass of breast cancer as ErbB2-positive that is frequently associated with poor prognosis. Current ErbB2-targeted therapies have profoundly improved patient outcomes, but mutations occurring in ErbB2 have been shown to confer drug resistance. Induction of ErbB2 degradation was proposed as an intriguing strategy to battle with ErbB2-positive breast cancer and reduced mutation-incurred drug resistance. Although multiple HSP90 inhibitors have been demonstrated to effectively trigger ErbB2 degradation, none succeeded in the clinical evaluations. To develop novel ErbB2-targeting strategies, we investigated the endocytic degradation and reversible ubiquitylation of ErbB2 in breast cancer. In this study, we reveal that HSP90 inhibition leads to efficient ubiquitylation and endocytic degradation of ErbB2 through the canonical endo-lysosomal route. USP2 associates with internalized ErbB2 and prevents its lysosomal sorting and degradation via exerting deubiquitylase activity. Accordingly, the USP2 inhibitor ML364 is capable of inducing ErbB2 ubiquitylation and accelerating its turnover. ML364 potentiates the pro-degradation effects of HSP90 inhibitors on ErbB2 and hence sensitizes ErbB2-positive breast cancer cells to HSP90 inhibition. The combination of USP2 and HSP90 inhibitors effectively restrains ErbB2-positive breast cancer xenograft growth in vivo. Based on these observations, we conclude that USP2 safeguards ErbB2 surface levels by antagonizing its ubiquitylation-mediated endocytic degradation, which can be exploited to design novel therapeutic strategies against ErbB2-driven malignancies as combinatorial treatment with HSP90 inhibitors.
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