ArticleThe Journal of biological chemistry2014
p75 neurotrophin receptor cleavage by α- and γ-secretases is required for neurotrophin-mediated proliferation of brain tumor-initiating cells.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 64 citations in OpenAlex.
- Nerve growth factor receptor (NGFR): A key player in glioblastoma progression.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Glycosylation-modulated conformational diversity in neurotrophin receptors.Biophysical journal · 2026Article
- Hallmarks of epithelial-mesenchymal plasticity in cancer.Molecular cancer · 2026Review
- Aberrant coupling of glutamate and tyrosine kinase receptors enables neuronal control of brain-tumor growth.Neuron · 2025Article
- Nerve growth factor: what can surgeons and oncologists learn from a neurological and psychological biomarker?Molecular medicine (Cambridge, Mass.) · 2025Review
- Oxidative Stress Suppresses Trk Signaling While Stimulating JNK-Mediated Endocytosis and Cleavage of p75Journal of neurochemistry · 2025Article
- miR-21 promotes cervical cancer by regulating NTF3.Scientific reports · 2025Article
- The clinical spectrum of central neurocytomas ranges from benign to leptomeningeal disseminating disease: a single institutional surgical series of 33 patients.Frontiers in surgery · 2025Article
- Nerve Growth Factor and the Role of Inflammation in Tumor Development.Current issues in molecular biology · 2024Review
- ProNGF Expression and Targeting in Glioblastoma Multiforme.International journal of molecular sciences · 2023Article
- Article
- LMO1 Plays an Oncogenic Role in Human Glioma Associated With NF-kB Pathway.Frontiers in oncology · 2022Article
- Bone Morphogenetic Protein 7 Effect on Human Glioblastoma Cell Transmigration and Migration.Life (Basel, Switzerland) · 2021Article
- The adaptive transition of glioblastoma stem cells and its implications on treatments.Signal transduction and targeted therapy · 2021Review
- The p75FEBS open bio · 2021Article
- Exportin 1 Inhibition Induces Nerve Growth Factor Receptor Expression to Inhibit the NF-κB Pathway in Preclinical Models of Pediatric High-Grade Glioma.Molecular cancer therapeutics · 2020Article
- Cancer stem cells-driven tumor growth and immune escape: the Janus face of neurotrophins.Aging · 2019Article
- Regulation of BACE1 expression after injury is linked to the p75 neurotrophin receptor.Molecular and cellular neurosciences · 2019Article
- Targetome Analysis Revealed Involvement of MiR-126 in Neurotrophin Signaling Pathway: A Possible Role in Prevention of Glioma Development.Cell journal · 2018Article
- Reciprocal Signaling between Glioblastoma Stem Cells and Differentiated Tumor Cells Promotes Malignant Progression.Cell stem cell · 2018Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Malignant gliomas are highly invasive, proliferative, and resistant to treatment. Previously, we have shown that p75 neurotrophin receptor (p75NTR) is a novel mediator of invasion of human glioma cells. However, the role of p75NTR in glioma proliferation is unknown. Here we used brain tumor-initiating cells (BTICs) and show that BTICs express neurotrophin receptors (p75NTR, TrkA, TrkB, and TrkC) and their ligands (NGF, brain-derived neurotrophic factor, and neurotrophin 3) and secrete NGF. Down-regulation of p75NTR significantly decreased proliferation of BTICs. Conversely, exogenouous NGF stimulated BTIC proliferation through α- and γ-secretase-mediated p75NTR cleavage and release of its intracellular domain (ICD). In contrast, overexpression of the p75NTR ICD induced proliferation. Interestingly, inhibition of Trk signaling blocked NGF-stimulated BTIC proliferation and p75NTR cleavage, indicating a role of Trk in p75NTR signaling. Further, blocking p75NTR cleavage attenuated Akt activation in BTICs, suggesting role of Akt in p75NTR-mediated proliferation. We also found that p75NTR, α-secretases, and the four subunits of the γ-secretase enzyme were elevated in glioblastoma multiformes patients. Importantly, the ICD of p75NTR was commonly found in malignant glioma patient specimens, suggesting that the receptor is activated and cleaved in patient tumors. These results suggest that p75NTR proteolysis is required for BTIC proliferation and is a novel potential clinical target.
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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 Socratic graph.