ArticleThe Journal of biological chemistry2015
Neurotrophin signaling via TrkB and TrkC receptors promotes the growth of brain tumor-initiating cells.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
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Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.
- Tracing the origins of glioblastoma by investigating the role of gliogenic and related neurogenic genes/signaling pathways in GBM development: a systematic review.World journal of surgical oncology · 2022Pooled it
- Trial
- Nerve growth factor receptor (NGFR): A key player in glioblastoma progression.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Macronutrients and micronutrients in relation to glioma: a bidirectional two-sample mendelian randomization analysis.Neurosurgical review · 2026Article
- Distinct molecular pathways leading to dosage-dependent temozolomide resistance in GBM stem cells.Cancer cell international · 2026Article
- Exploring the Neurobiological Mechanisms of Cancer Growth.Current pharmaceutical design · 2026Review
- Glioblastoma pathophysiology: roles of aging driven changes in STAT3 interactions with NF-κB dimer components in the modulation of the mitochondrial melatonergic pathway and night-time inflammation resolution.Exploration of targeted anti-tumor therapy · 2026Review
- A Prognostic Neuromodulation-Related Gene Signature Identifies Immunomodulation and Tumour-Associated Hallmarks in Glioblastoma.Biomedicines · 2025Article
- Updated Insights into the Molecular Pathophysiology of Olfactory Neuroblastoma Using Multi-Omics Analysis.Journal of personalized medicine · 2025Review
- Cancer-nervous system crosstalk: from biological mechanism to therapeutic opportunities.Molecular cancer · 2025Review
- Role of TRKC and NT-3 proteins in the progression and prognosis of colorectal cancer.Translational cancer research · 2025Article
- Atypical cellular responses mediated by intracellular constitutive active TrkB (NTRK2) kinase domains and a solely intracellular NTRK2-fusion oncogene.Cancer gene therapy · 2024Article
- The oncogenic fusion protein EML4-NTRK3 requires three salt bridges for stability and biological activity.Heliyon · 2024Article
- Glioblastoma microenvironment-from biology to therapy.Genes & development · 2024Review
- AAV-mediated gene therapies for glaucoma and uveitis: are we there yet?Expert reviews in molecular medicine · 2024Review
- Periampullary cancer and neurological interactions: current understanding and future research directions.Frontiers in oncology · 2024Review
- Tropomyosin receptor kinase B (TrkB) signalling: targeted therapy in neurogenic tumours.The journal of pathology. Clinical research · 2023Review
- Neurons as stromal drivers of nervous system cancer formation and progression.Developmental cell · 2023Review
- Biomimetic three-dimensional glioma model printedInternational journal of bioprinting · 2023Article
- Novel Design of RNA Aptamers as Cancer Inhibitors and Diagnosis Targeting the Tyrosine Kinase Domain of the NT-3 Growth Factor Receptor Using a Computational Sequence-Based Approach.Molecules (Basel, Switzerland) · 2022Article
23 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Neurotrophins and their receptors are frequently expressed in malignant gliomas, yet their functions are largely unknown. Previously, we have shown that p75 neurotrophin receptor is required for glioma invasion and proliferation. However, the role of Trk receptors has not been examined. In this study, we investigated the importance of TrkB and TrkC in survival of brain tumor-initiating cells (BTICs). Here, we show that human malignant glioma tissues and also tumor-initiating cells isolated from fresh human malignant gliomas express the neurotrophin receptors TrkB and TrkC, not TrkA, and they also express neurotrophins NGF, BDNF, and neurotrophin 3 (NT3). Specific activation of TrkB and TrkC receptors by ligands BDNF and NT3 enhances tumor-initiating cell viability through activation of ERK and Akt pathways. Conversely, TrkB and TrkC knockdown or pharmacologic inhibition of Trk signaling decreases neurotrophin-dependent ERK activation and BTIC growth. Further, pharmacological inhibition of both ERK and Akt pathways blocked BDNF, and NT3 stimulated BTIC survival. Importantly, attenuation of BTIC growth by EGFR inhibitors could be overcome by activation of neurotrophin signaling, and neurotrophin signaling is sufficient for long term BTIC growth as spheres in the absence of EGF and FGF. Our results highlight a novel role for neurotrophin signaling in brain tumor and suggest that Trks could be a target for combinatorial treatment of malignant glioma.
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Registered trials
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.