ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Neuroblastoma phox2b variants stimulate proliferation and dedifferentiation of immature sympathetic neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 59 citations in OpenAlex.
- Redefining PHOX2B-Related Neurodevelopmental Disorders as Circuitopathies: A New Paradigm in Autonomic Network Medicine.Neuroscience bulletin · 2026Review
- The Role of Precision Medicine in Neuroblastoma: Targeted Therapies and Personalized Approaches-A Narrative Review.Health science reports · 2026Article
- CRISPR/Cas9-mediatedFrontiers in physiology · 2026Article
- Regulation and dysregulation of microRNA - transcription factor axes in differentiation and neuroblastoma.Cellular and molecular life sciences : CMLS · 2025Review
- Revisiting Neuroblastoma: Nrf2, NF-κB and Phox2B as a Promising Network in Neuroblastoma.Current issues in molecular biology · 2024Review
- NAMPT Inhibition Induces Neuroblastoma Cell Death and Blocks Tumor Growth.Frontiers in oncology · 2022Article
- The sympathies of the body: functional organization and neuronal differentiation in the peripheral sympathetic nervous system.Cell and tissue research · 2021Review
- A Focus on Regulatory Networks Linking MicroRNAs, Transcription Factors and Target Genes in Neuroblastoma.Cancers · 2021Review
- Neuroblastoma differentiation in vivo excludes cranial tumors.Developmental cell · 2021Article
- Review
- Identification and Functional Validation of Radioresistance-Related GenesOncoTargets and therapy · 2021Article
- Transcription Factors Phox2a/2b Upregulate Expression of Noradrenergic and Dopaminergic Phenotypes in Aged Rat Brains.Neurotoxicity research · 2020Article
- Research Advances on Therapeutic Approaches to Congenital Central Hypoventilation Syndrome (CCHS).Frontiers in neuroscience · 2020Review
- Integrative analysis identifies lincRNAs up- and downstream of neuroblastoma driver genes.Scientific reports · 2019Article
- Neuroblastoma-A Neural Crest Derived Embryonal Malignancy.Frontiers in molecular neuroscience · 2019Review
- From proliferation to target innervation: signaling molecules that direct sympathetic nervous system development.Cell and tissue research · 2018Review
- Neuroblastoma pathogenesis: deregulation of embryonic neural crest development.Cell and tissue research · 2018Review
- Enhancer invasion shapes MYCN-dependent transcriptional amplification in neuroblastoma.Nature genetics · 2018Article
- Structural and functional differences in PHOX2B frameshift mutations underlie isolated or syndromic congenital central hypoventilation syndrome.Human mutation · 2018Article
- Heterogeneity of neuroblastoma cell identity defined by transcriptional circuitries.Nature genetics · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroblastoma is a pediatric tumor that is thought to arise from autonomic precursors in the neural crest. Mutations in the PHOX2B gene have been observed in familial and sporadic forms of neuroblastoma and represent the first defined genetic predisposition for neuroblastoma. Here, we address the mechanisms that may underlie this predisposition, comparing the function of wild-type and mutant Phox2b proteins ectopically expressed in proliferating, embryonic sympathetic neurons. Phox2b displays a strong antiproliferative effect, which is lost in all Phox2b neuroblastoma variants analyzed. In contrast, an increase in sympathetic neuron proliferation is elicited by Phox2b variants with mutations in the homeodomain when endogenous Phox2b levels are lowered by siRNA-mediated knockdown to mimic the situation of heterozygous PHOX2B mutations in neuroblastoma. The increased proliferation is blocked by Hand2 knockdown and the antiproliferative Phox2b effects are rescued by Hand2 overexpression, implying Hand2 in Phox2b-mediated proliferation control. A Phox2b variant with a nonsense mutation in the homeodomain elicits, in addition, a decreased expression of characteristic marker genes. Together, these results suggest that PHOX2B mutations predispose to neuroblastoma by increasing proliferation and promoting dedifferentiation of cells in the sympathoadrenergic lineage.
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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.