ArticleNature cancer2020
Sonic hedgehog accelerates DNA replication to cause replication stress promoting cancer initiation in medulloblastoma.
Article in Nature cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Paediatric therapeutic development workshop on medulloblastoma.British journal of cancer · 2026Review
- Ubiquitin-dependent degradation of p27Kip1 and p21Waf1/Cip1 by AMBRA1 ensures G1 and S phase progression and limits replication stress.Nucleic acids research · 2026Article
- Morphogen Gradients as Drivers of Mosaicism During Early Human Development.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Arhgef7 is essential for granule cell precursor proliferation and migration during cerebellum development.iScience · 2026Article
- The need for speed: drivers and consequences of accelerated replication forks.Communications biology · 2025Review
- Targeting the crosstalk of metabolism reprogramming and replication stress: novel strategy to combat cancer.Medical oncology (Northwood, London, England) · 2025Review
- G-quadruplexes as a source of vulnerability in BRCA2Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Genetic modeling of ELP1-associated Sonic hedgehog medulloblastoma identifies MDM2 as a selective therapeutic target.Cancer cell · 2025Article
- Dissecting the Impact of Genetic Background on Oncogenic Response to Radiation Exposure in theCells · 2024Article
- Developmental signals control chromosome segregation fidelity during pluripotency and neurogenesis by modulating replicative stress.Nature communications · 2024Article
- Numb positively regulates Hedgehog signaling at the ciliary pocket.Nature communications · 2024Article
- Childhood cancer mutagenesis caused by transposase-derived PGBD5.Science advances · 2024Article
- PTCH1-mutant human cerebellar organoids exhibit altered neural development and recapitulate early medulloblastoma tumorigenesis.Disease models & mechanisms · 2024Article
- Critical DNA damaging pathways in tumorigenesis.Seminars in cancer biology · 2022Review
- Topoisomerase 1-dependent R-loop deficiency drives accelerated replication and genomic instability.Cell reports · 2022Article
- Meier-Gorlin Syndrome: Clinical Misdiagnosis, Genetic Testing and Functional Analysis ofInternational journal of molecular sciences · 2022Article
- Sonic Hedgehog Signaling in Cerebellar Development and Cancer.Frontiers in cell and developmental biology · 2022Review
- MCM complex members MCM3 and MCM7 are associated with a phenotypic spectrum from Meier-Gorlin syndrome to lipodystrophy and adrenal insufficiency.European journal of human genetics : EJHG · 2021Article
- Effects of IGF-1 on Proliferation, Angiogenesis, Tumor Stem Cell Populations and Activation of AKT and Hedgehog Pathways in Oral Squamous Cell Carcinoma.International journal of molecular sciences · 2020Article
- The Role of γH2AX in Replication Stress-induced Carcinogenesis: Possible Links and Recent Developments.Cancer diagnosis & prognosisReview
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The mechanisms generating cancer-initiating mutations are not well understood. Sonic hedgehog (SHH) pathway activation is frequent in medulloblastoma (MB), with PTCH1 mutations being a common initiating event. Here we investigated the role of the developmental mitogen SHH in initiating carcinogenesis in the cells of origin: granule cell progenitors (GCPs). We delineate a molecular mechanism for tumor initiation in MB. Exposure of GCPs to Shh causes a distinct form of DNA replication stress, increasing both origin firing and fork velocity. Shh promotes DNA helicase loading and activation, with increased Cdc7-dependent origin firing. The S-phase duration is reduced and hyper-recombination occurs, causing copy number neutral loss of heterozygosity-a frequent event at the PTCH1/ptch1 locus. Moreover, Cdc7 inhibition to attenuate origin firing reduces recombination and preneoplastic tumor formation in mice. Therefore, tissue-specific replication stress induced by Shh promotes loss of heterozygosity, which in tumor-prone Ptch1
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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.