ArticleOncogene2023
Deubiquitylation of Rab35 by USP32 promotes the transmission of imatinib resistance by enhancing exosome secretion in gastrointestinal stromal tumours.
Article in Oncogene, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Deubiquitination of Vangl by USP6 and USP32 Regulates Planar Cell Polarity Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Deubiquitinase USP32 stabilizes DDX17 to promote tumor progression and lenvatinib resistance in hepatocellular carcinoma via the miR-3163/MAPK pathway.Cell death & disease · 2026Article
- Genetic Variations in the M6A Modification Pathway as Potential Predictors of Imatinib Secondary Resistance in Gastrointestinal Stromal Tumors.Journal of clinical medicine · 2026Article
- Targeted Therapy for Advanced Gastrointestinal Stromal Tumors: Evolution and Future Directions.Drug design, development and therapy · 2026Review
- Phosphorylation of USP32 by CDK5 regulates Rap1 stability and therapeutic resistance in pancreatic ductal adenocarcinoma.Oncogene · 2025Article
- The E3 Ubiquitin Ligase ARIH1 Facilitates Colorectal Cancer Progression by Promoting Oxidative Phosphorylation via the Mitochondrial Translocation of K63-Linked Ubiquitinated PHB1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Exosome-Mediated Chemoresistance in Cancers: Mechanisms, Therapeutic Implications, and Future Directions.Biomolecules · 2025Review
- Lycobetaine Has Therapeutic Efficacy in Lung Squamous Cell Carcinoma by Targeting USP32 to Trigger Ferroptosis.Current issues in molecular biology · 2025Article
- The effect of ubiquitination and deubiquitination to imatinib resistance in gastrointestinal stromal tumors.Frontiers in oncology · 2025Review
- Biogenesis of Extracellular Vesicles (EVs) and the Potential Use of Embryo-Derived EVs in Medically Assisted Reproduction.International journal of molecular sciences · 2024Review
- Extracellular Vesicles from Compression-Loaded Cementoblasts Promote the Tissue Repair Function of Macrophages.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- USP32 facilitates non-small cell lung cancer progression via deubiquitinating BAG3 and activating RAF-MEK-ERK signaling pathway.Oncogenesis · 2024Article
- Drug resistance mechanisms and treatment strategies mediated by Ubiquitin-Specific Proteases (USPs) in cancers: new directions and therapeutic options.Molecular cancer · 2024Review
- RAB42 overexpression correlates with poor prognosis, immune cell infiltration and chemoresistance.Frontiers in pharmacology · 2024Article
- High USP32 expression contributes to cancer progression and is correlated with immune infiltrates in hepatocellular carcinoma.BMC cancer · 2023Article
- Exosomes in Cancer Progression and Therapy Resistance: Molecular Insights and Therapeutic Opportunities.Life (Basel, Switzerland) · 2023Review
- USP32 deubiquitinase: cellular functions, regulatory mechanisms, and potential as a cancer therapy target.Cell death discovery · 2023Review
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Imatinib is a tyrosine kinase inhibitor that is widely used to combat gastrointestinal stromal tumours (GISTs). However, secondary resistance to imatinib is an important challenge in GIST treatment. Recent studies have demonstrated that cancer-derived nanosized exosomes play a key role in intercellular communication, but little is known about the roles of exosomes in imatinib-resistant GISTs. Here, we reveal that exosomes released from imatinib-resistant GISTs transmit drug resistance to imatinib-sensitive tumours. By using iTRAQ technology, we demonstrate that Ras-related protein Rab-35 (Rab35) is upregulated differentially in imatinib-resistant GISTs. Loss of Rab35 decreases exosome secretion, thereby hampering the transmission of imatinib resistance to sensitive tumours. Mechanistically, we showed that the ubiquitin‒proteasome system is involved in elevated Rab35 expression and that ubiquitin-specific protease 32 (USP32), a deubiquitylating enzyme, is bound to Rab35. Further experiments demonstrate that this protease protects Rab35 from proteasomal degradation by reducing Lys48 (K48)-ubiquitination. Additionally, we found that the transcription factor ETV1, which is a lineage survival factor in GISTs, promotes USP32 expression. Collectively, our results reveal that exosomes transmit imatinib resistance in GISTs and that deubiquitylation plays a key role in regulating the transmission process. The USP32-Rab35 axis provides a potential target for interventions to reduce the occurrence of imatinib resistance in GISTs.
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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.