ArticleThe Journal of clinical investigation2013
Dependence receptor UNC5D mediates nerve growth factor depletion-induced neuroblastoma regression.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 52 citations in OpenAlex.
- Review
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- Joint analysis of the metabolomics and transcriptomics uncovers the dysregulated network and develops the diagnostic model of high-risk neuroblastoma.Scientific reports · 2023Article
- The genetics of autism spectrum disorder in an East African familial cohort.Cell genomics · 2023Article
- Ebola Virus Encodes Two microRNAs in Huh7-Infected Cells.International journal of molecular sciences · 2022Article
- Promoter methylation-mediated repression of UNC5 receptors and the associated clinical significance in human colorectal cancer.Clinical epigenetics · 2021Article
- The Prevailing Role of Topoisomerase 2 Beta and its Associated Genes in Neurons.Molecular neurobiology · 2021Review
- Dependence receptors: new targets for cancer therapy.EMBO molecular medicine · 2021Review
- Exome sequencing identifies somatic mutations in novel driver genes in non-small cell lung cancer.Aging · 2020Observational
- Spontaneous regression of stage III neuroblastoma: A case report.World journal of clinical cases · 2020Article
- UNC5D, suppressed by promoter hypermethylation, inhibits cell metastasis by activating death-associated protein kinase 1 in prostate cancer.Cancer science · 2019Article
- Copy number changes at 8p11-12 predict adverse clinical outcome and chemo- and radiotherapy response in breast cancer.Oncotarget · 2018Article
- Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.Cell death and differentiation · 2018Review
- Tumor-suppressive function ofOncotarget · 2017Article
- Nerve growth factor and its receptors on onset and diagnosis of ovarian cancer.Oncology letters · 2017Article
- Inhibition of DNA methylation promotes breast tumor sensitivity to netrin-1 interference.EMBO molecular medicine · 2016Article
- The "neuro" of neuroblastoma: Neuroblastoma as a neurodevelopmental disorder.Annals of neurology · 2016Review
- Review
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spontaneous regression of neuroblastoma (NB) resembles the developmentally regulated programmed cell death (PCD) of sympathetic neurons. Regressing tumor cells express high levels of the nerve growth factor (NGF) receptors TRKA and p75NTR and are dependent on NGF for survival; however, the underlying molecular mechanism remains elusive. Here, we show that UNC5D, a dependence receptor that is directly targeted by p53 family members, is highly expressed in favorable NBs. NGF withdrawal strongly upregulated UNC5D, E2F1, and p53 in human primary favorable NBs. The induced UNC5D was cleaved by caspases 2/3, and the released intracellular fragment translocated into the nucleus and interacted with E2F1 to selectively transactivate the proapoptotic target gene. The cleavage of UNC5D and its induction of apoptosis were strongly inhibited by addition of netrin-1. Unc5d(-/-) mice consistently exhibited a significant increase in dorsal root ganglia neurons and resistance to NGF depletion-induced apoptosis in sympathetic neurons compared with wild-type cells. Our data suggest that UNC5D forms a positive feedback loop with p53 and E2F1 to promote NGF dependence-mediated PCD during NB regression.
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