ArticleOncogene2009
Patched1 deletion increases N-Myc protein stability as a mechanism of medulloblastoma initiation and progression.
Article in Oncogene, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Sonic hedgehog signalling pathway in CNS tumours: its role and therapeutic implications.Molecular brain · 2024Review
- Molecular mechanisms of neuroendocrine differentiation in prostate cancer progression.Journal of cancer research and clinical oncology · 2022Review
- Three dimensional reconstruction of the mouse cerebellum in Hedgehog-driven medulloblastoma models to identify Norrin-dependent effects on preneoplasia.Communications biology · 2022Article
- Basal cell carcinomas acquire secondary mutations to overcome dormancy and progress from microscopic to macroscopic disease.Cell reports · 2022Article
- Polymeric nanomedicine for overcoming resistance mechanisms in hedgehog and Myc-amplified medulloblastoma.Biomaterials · 2021Article
- The Role of Notch, Hedgehog, and Wnt Signaling Pathways in the Resistance of Tumors to Anticancer Therapies.Frontiers in cell and developmental biology · 2021Review
- Transcriptional repressor REST drives lineage stage-specific chromatin compaction atScience signaling · 2019Article
- Wnt, Notch, and TGF-β Pathways Impinge on Hedgehog Signaling Complexity: An Open Window on Cancer.Frontiers in genetics · 2019Review
- Medulloblastoma, WNT-activated/SHH-activated: clinical impact of molecular analysis and histogenetic evaluation.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2018Review
- Deletion of sphingosine kinase 1 inhibits liver tumorigenesis in diethylnitrosamine-treated mice.Oncotarget · 2018Article
- Primary Cilia in the Murine Cerebellum and in Mutant Models of Medulloblastoma.Cellular and molecular neurobiology · 2017Article
- SHH desmoplastic/nodular medulloblastoma and Gorlin syndrome in the setting of Down syndrome: case report, molecular profiling, and review of the literature.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2016Review
- PERK Activation Promotes Medulloblastoma Tumorigenesis by Attenuating Premalignant Granule Cell Precursor Apoptosis.The American journal of pathology · 2016Article
- In vivo Mn-enhanced MRI for early tumor detection and growth rate analysis in a mouse medulloblastoma model.Neoplasia (New York, N.Y.) · 2014Article
- Oncoprotein stabilization in brain tumors.Oncogene · 2014Review
- Drugging MYCN through an allosteric transition in Aurora kinase A.Cancer cell · 2014Article
- The prenatal origins of cancer.Nature reviews. Cancer · 2014Review
- Role of MYC in Medulloblastoma.Cold Spring Harbor perspectives in medicine · 2013Review
- NPV-LDE-225 (Erismodegib) inhibits epithelial mesenchymal transition and self-renewal of glioblastoma initiating cells by regulating miR-21, miR-128, and miR-200.Neuro-oncology · 2013Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Medulloblastoma tumorigenesis caused by inactivating mutations in the PATCHED1 (PTCH1) gene is initiated by persistently activated Sonic Hedgehog (Shh) signaling in granule neuron precursors (GNPs) during the late stages of cerebellar development. Both normal cerebellar development and Shh-driven medulloblastoma tumorigenesis require N-Myc expression. However, the mechanisms by which N-Myc affects the stages of medulloblastoma initiation and progression are unknown. Here we used a mouse model of Ptch1 heterozygosity and medulloblastoma to show that increased N-Myc expression characterized the earliest selection of focal GNP hyperplasia destined for later tumor progression. Step-wise loss of Ptch1 expression, from tumor initiation to progression, led to incremental increases in N-Myc protein, rather than mRNA, expression. Increased N-Myc resulted in enhanced proliferation and death resistance of perinatal GNPs at tumor initiation. Sequential N-Myc protein phosphorylation at serine-62 and serine-62/threonine-58 characterized the early and late stages of medulloblastoma tumorigenesis, respectively. Shh pathway activation led to increased Myc protein stability and reduced expression of key regulatory factors. Taken together our data identify N-Myc protein stability as the result of loss of Ptch1, which distinguishes normal cerebellar development from medulloblastoma tumorigenesis.
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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.