ArticleOncotarget2018
TrkAIII signals endoplasmic reticulum stress to the mitochondria in neuroblastoma cells, resulting in glycolytic metabolic adaptation.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 12 citations in OpenAlex.
- Article
- Review
- A novel PGK1 activator improves Alzheimer's disease by regulating glycolysis.Alzheimer's research & therapy · 2026Article
- Jurkat T-Cell Antigen-Independent Elimination of PMA-Activated Neuroblastoma Cells Is Triggered by CCL2/CCR2, Depends Upon Lipid Raft LFA1/ICAM1 Immune Synapses, Is Mediated by m-TRAIL and Is Augmented by the TrkAIII Oncoprotein.International journal of molecular sciences · 2026Article
- Article
- 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
- A Study of Alternative TrkA Splicing Identifies TrkAIII as a Novel Potentially Targetable Participant in PitNET Progression.Biology · 2024Article
- Article
- Nutraceutical Preventative and Therapeutic Potential in Neuroblastoma: From Pregnancy to Early Childhood.Life (Basel, Switzerland) · 2022Review
- Mechanisms involved in selecting and maintaining neuroblastoma cancer stem cell populations, and perspectives for therapeutic targeting.World journal of stem cells · 2021Review
- Hypoxia-induced alternative splicing: the 11th Hallmark of Cancer.Journal of experimental & clinical cancer research : CR · 2020Review
- A pilot study of alternative TrkAIII splicing in Merkel cell carcinoma: a potential oncogenic mechanism and novel therapeutic target.Journal of experimental & clinical cancer research : CR · 2019Article
- Two Receptors, Two Isoforms, Two Cancers: Comprehensive Analysis of KIT and TrkA Expression in Neuroblastoma and Acute Myeloid Leukemia.Frontiers in oncology · 2019Article
- The oncogenic neurotrophin receptor tropomyosin-related kinase variant, TrkAIII.Journal of experimental & clinical cancer research : CR · 2018Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alternative TrkAIII splicing characterises advanced stage metastatic disease and post-therapeutic relapse in neuroblastoma (NB), and in NB models TrkAIII exhibits oncogenic activity. In this study, we report a novel role for TrkAIII in signaling ER stress to the mitochondria in SH-SY5Y NB cells that results in glycolytic metabolic adaptation. The ER stress-inducing agents DTT, A23187 and thapsigargin activated the ER stress-response in control pcDNA SH-SY5Y and TrkAIII expressing SH-SY5Y cells and in TrkAIII SH-SY5Y cells increased TrkAIII targeting to mitochondria and internalisation into inner-mitochondrial membranes. Within inner-mitochondrial membranes, TrkAIII was subjected to Omi/HtrA2-dependent cleavage to tyrosine phosphorylated 45-48kDa carboxyl terminal active fragments, localised predominantly in tyrosine kinase-domain mitochondrial matrix orientation. This stress-induced activation of mitochondrial TrkAIII was associated with increased ROS production, prevented by the ROS scavenger Resveratrol and underpinned by changes in Ca2+ movement, implicating ROS/Ca2+ interplay in overcoming the mitochondrial TrkAIII activation threshold. Stress-induced, cleavage-activation of mitochondrial TrkAIII resulted in mitochondrial PDHK1 tyrosine phosphorylation, leading to glycolytic metabolic adaptation. This novel mitochondrial role for TrkAIII provides a potential self-perpetuating, drug reversible way through which tumour microenvironmental stress may maintain the metastasis promoting "Warburg effect" in TrkAIII expressing NBs.
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