ArticleCancer2013
UBE4B levels are correlated with clinical outcomes in neuroblastoma patients and with altered neuroblastoma cell proliferation and sensitivity to epidermal growth factor receptor inhibitors.
Article in Cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- TGFβ signaling sensitizes MEKi-resistant human melanoma to targeted therapy-induced apoptosis.Cell death & disease · 2024Article
- Targeting the ubiquitin-proteasome system: a novel therapeutic strategy for neuroblastoma.Frontiers in oncology · 2024Review
- UBE4B interacts with the ITCH E3 ubiquitin ligase to induce Ku70 and c-FLIPL polyubiquitination and enhanced neuroblastoma apoptosis.Cell death & disease · 2023Article
- Identification of a novel gene signature for neuroblastoma differentiation using a Boolean implication network.Genes, chromosomes & cancer · 2023Article
- Fine-tuning of mTOR signaling by the UBE4B-KLHL22 E3 ubiquitin ligase cascade in brain development.Development (Cambridge, England) · 2022Article
- SF3B4 Depletion Retards the Growth of A549 Non-Small Cell Lung Cancer Cells via UBE4B-Mediated Regulation of p53/p21 and p27 Expression.Molecules and cells · 2022Article
- Allele-specific expression reveals genes with recurrent cis-regulatory alterations in high-risk neuroblastoma.Genome biology · 2022Article
- Development of FeCancer nanotechnology · 2021Article
- The ubiquitin ligase UBE4B regulates amyloid precursor protein ubiquitination, endosomal trafficking, and amyloid β42 generation and secretion.Molecular and cellular neurosciences · 2020Article
- MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy.Cancers · 2020Review
- The Roles of Ubiquitination Factor E4B (UBE4B) in the Postoperative Prognosis of Patients with Renal Cell Carcinoma and in Renal Tumor Cells Growth and Metastasis.OncoTargets and therapy · 2020Article
- Regulation of the p53 Family Proteins by the Ubiquitin Proteasomal Pathway.International journal of molecular sciences · 2019Review
- Review
- Cellular components in tumor microenvironment of neuroblastoma and the prognostic value.PeerJ · 2019Article
- Silencing UBE4B induces nasopharyngeal carcinoma apoptosis through the activation of caspase3 and p53.OncoTargets and therapy · 2019Article
- Low UBE4B expression increases sensitivity of chemoresistant neuroblastoma cells to EGFR and STAT5 inhibition.Cancer biology & therapy · 2019Article
- The identification of novel regions for reproduction trait in Landrace and Large White pigs using a single step genome-wide association study.Asian-Australasian journal of animal sciences · 2018Article
- Identification of Potential Prognostic Genes for Neuroblastoma.Frontiers in genetics · 2018Article
- E4 ligase-specific ubiquitination hubs coordinate DNA double-strand-break repair and apoptosis.Nature structural & molecular biology · 2016Article
- Binimetinib inhibits MEK and is effective against neuroblastoma tumor cells with low NF1 expression.BMC cancer · 2016Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe UBE4B gene, which is located on chromosome 1p36, encodes a ubiquitin ligase that interacts with hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs), a protein involved in epidermal growth factor receptor (EGFR) trafficking, suggesting a link between EGFR trafficking and neuroblastoma pathogenesis. The authors analyzed the roles of UBE4B in the outcomes of patients with neuroblastoma and in neuroblastoma tumor cell proliferation, EGFR trafficking, and response to EGFR inhibition.
methodsThe association between UBE4B expression and the survival of patients with neuroblastoma was examined using available microarray data sets. UBE4B and EGFR protein levels were measured in patient tumor samples, EGFR degradation rates were measured in neuroblastoma cell lines, and the effects of UBE4B on neuroblastoma tumor cell growth were analyzed. The effects of the EGFR inhibitor cetuximab were examined in neuroblastoma cells that expressed wild-type and mutant UBE4B.
resultsLow UBE4B gene expression is associated with poor outcomes in patients with neuroblastoma. UBE4B overexpression reduced neuroblastoma tumor cell proliferation, and UBE4B expression was inversely related to EGFR expression in tumor samples. EGFR degradation rates correlated with cellular UBE4B levels. Enhanced expression of catalytically active UBE4B resulted in reduced sensitivity to EGFR inhibition.
conclusionsThe current study demonstrates associations between UBE4B expression and the outcomes of patients with neuroblastoma and between UBE4B and EGFR expression in neuroblastoma tumor samples. Moreover, levels of UBE4B influence neuroblastoma tumor cell proliferation, EGFR degradation, and response to EGFR inhibition. These results suggest UBE4B-mediated growth factor receptor trafficking may contribute to the poor prognosis of patients who have neuroblastoma tumors with 1p36 deletions and that UBE4B expression may be a marker that can predict responses of neuroblastoma tumors to treatment.
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