ArticleOncogene2009
The neuroblastoma tumour-suppressor TrkAI and its oncogenic alternative TrkAIII splice variant exhibit geldanamycin-sensitive interactions with Hsp90 in human neuroblastoma cells.
Article in Oncogene, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Advances in Targeting Growth Factor Signalling in Neuroblastoma and Overcoming Drug Resistance.Cells · 2025Review
- Molecular Characterization and Inhibition of a Novel Stress-Induced Mitochondrial Protecting Role for Misfolded TrkAIII in Human SH-SY5Y Neuroblastoma Cells.International journal of molecular sciences · 2024Article
- Article
- Doxorubicin-Induced TrkAIII Activation: A Selection Mechanism for Resistant Dormant Neuroblastoma Cells.International journal of molecular sciences · 2022Article
- Hypoxia-induced alternative splicing: the 11th Hallmark of Cancer.Journal of experimental & clinical cancer research : CR · 2020Review
- The oncogenic neurotrophin receptor tropomyosin-related kinase variant, TrkAIII.Journal of experimental & clinical cancer research : CR · 2018Review
- TrkAIII signals endoplasmic reticulum stress to the mitochondria in neuroblastoma cells, resulting in glycolytic metabolic adaptation.Oncotarget · 2018Article
- Article
- Retrograde TrkAIII transport from ERGIC to ER: a re-localisation mechanism for oncogenic activity.Oncotarget · 2015Article
- TrkA is amplified in malignant melanoma patients and induces an anti-proliferative response in cell lines.BMC cancer · 2015Article
- Proteolytic cleavage, trafficking, and functions of nuclear receptor tyrosine kinases.The FEBS journal · 2015Review
- Article
- Molecular mechanism of 17-allylamino-17-demethoxygeldanamycin (17-AAG)-induced AXL receptor tyrosine kinase degradation.The Journal of biological chemistry · 2013Article
- TrkAIII promotes microtubule nucleation and assembly at the centrosome in SH-SY5Y neuroblastoma cells, contributing to an undifferentiated anaplastic phenotype.BioMed research international · 2013Article
- k-Nearest neighbor models for microarray gene expression analysis and clinical outcome prediction.The pharmacogenomics journal · 2010Article
- Heat shock protein 90 inhibition depletes TrkA levels and signaling in human acute leukemia cells.Molecular cancer therapeutics · 2010Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hsp90 chaperones stabilize many tyrosine kinases including several oncogenes, which are inhibited or induced to degrade by the Hsp90 inhibitor geldanamycin (GA). As a consequence, GA has been developed for future chemotherapeutic use in several tumour types including neuroblastoma (NB). Alternative splicing of the neurotrophin receptor tyrosine kinase TrkA may have a pivotal function in regulating NB behaviour, with reports suggesting that tumour-suppressing signals from TrkA may be converted to oncogenic signals by stress-regulated alternative TrkAIII splicing. Within this context, it is important to know whether Hsp90 interacts with TrkA variants in NB cells and how GA influences this. Here, we report that both TrkAI and TrkAIII are Hsp90 clients in human NB cells. TrkAI exhibits GA-sensitive interaction with Hsp90 required for receptor endoplasmic reticulum export, maturation, cell surface stabilization and ligand-mediated activation, whereas TrkAIII exhibits GA-sensitive interactions with Hsp90 required for spontaneous activity and to a lesser extent stability. We show that GA inhibits proliferation and induces apoptosis of TrkAI expressing NB cells, whereas TrkAIII reduces the sensitivity of NB cells to GA-induced elimination. Our data suggest that GA-sensitive interactions with Hsp90 are critical for both TrkAI tumour suppressor and TrkAIII oncogenic function in NB and that TrkAIII expression exerts a negative impact on GA-induced NB cell eradication, which can be counteracted by a novel TrkAIII-specific peptide nucleic acid inhibitor.
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