ArticleOncogene2013
Bax deficiency prolongs cerebellar neurogenesis, accelerates medulloblastoma formation and paradoxically increases both malignancy and differentiation.
Article in Oncogene, 2013. 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 25 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.
The trial behind it
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
25 citing papers in PubMed, 37 citations in OpenAlex.
- Programmed cell death and melatonin: A comprehensive review.Functional & integrative genomics · 2024Review
- The pivotal role of irradiation-induced apoptosis in the pathogenesis and therapy of medulloblastoma.Cancer reports (Hoboken, N.J.) · 2024Review
- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- PRC2 disruption in cerebellar progenitors produces cerebellar hypoplasia and aberrant myoid differentiation without blocking medulloblastoma growth.Acta neuropathologica communications · 2023Article
- Automated Immunofluorescence Staining for Analysis of DNA Damage and Apoptosis in Brain Sections.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Brain milieu induces early microglial maturation through the BAX-Notch axis.Nature communications · 2022Article
- The role of Bcl-2 proteins in modulating neuronal CaBiochimica et biophysica acta. Molecular cell research · 2021Review
- Antiapoptotic Bcl-2 family proteins BCL-xL and MCL-1 integrate neural progenitor survival and proliferation during postnatal cerebellar neurogenesis.Cell death and differentiation · 2021Article
- Brain Tumor Microenvironment and Angiogenesis in Melanoma Brain Metastases.Frontiers in oncology · 2020Article
- scRNA-seq in medulloblastoma shows cellular heterogeneity and lineage expansion support resistance to SHH inhibitor therapy.Nature communications · 2019Article
- Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins.Nature reviews. Molecular cell biology · 2019Review
- Detection of pro-apoptotic Bax∆2 proteins in the human cerebellum.Histochemistry and cell biology · 2018Article
- Selective BCL-XL inhibition promotes apoptosis in combination with MLN8237 in medulloblastoma and pediatric glioblastoma cells.Neuro-oncology · 2018Article
- Molecular Basis of Pediatric Brain Tumors.Neuromolecular medicine · 2017Review
- Geminin deficiency enhances survival in a murine medulloblastoma model by inducing apoptosis of preneoplastic granule neuron precursors.Genes & cancer · 2017Article
- Pyruvate Kinase Inhibits Proliferation during Postnatal Cerebellar Neurogenesis and Suppresses Medulloblastoma Formation.Cancer research · 2017Article
- ATR maintains chromosomal integrity during postnatal cerebellar neurogenesis and is required for medulloblastoma formation.Development (Cambridge, England) · 2016Article
- Radiation Sensitivity in a Preclinical Mouse Model of Medulloblastoma Relies on the Function of the Intrinsic Apoptotic Pathway.Cancer research · 2016Article
- Aspm sustains postnatal cerebellar neurogenesis and medulloblastoma growth in mice.Development (Cambridge, England) · 2015Article
- Mitotic events in cerebellar granule progenitor cells that expand cerebellar surface area are critical for normal cerebellar cortical lamination in mice.Journal of neuropathology and experimental neurology · 2015Article
Corrections and comments
- Erratum issuedBax deficiency prolongs cerebellar neurogenesis, accelerates medulloblastoma formation and paradoxically increases both malignancy and differentiation.2015 · Miller, C Ryan [Corrected to Miller, C R]
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Neurogenesis requires negative regulation through differentiation of progenitors or their programmed cell death (PCD). Growth regulation is particularly important in the postnatal cerebellum, where excessive progenitor proliferation promotes medulloblastoma, the most common malignant brain tumor in children. We present evidence that PCD operates alongside differentiation to regulate cerebellar granule neuron progenitors (CGNPs) and to prevent medulloblastoma. Here, we show that genetic deletion of pro-apoptotic Bax disrupts regulation of cerebellar neurogenesis and promotes medulloblastoma formation. In Bax(-/-) mice, the period of neurogenesis was extended into the third week of postnatal life, and ectopic neurons and progenitors collected in the molecular layer of the cerebellum and adjacent tectum. Importantly, genetic deletion of Bax in medulloblastoma-prone ND2:SmoA1 transgenic mice greatly accelerated tumorigenesis. Bax-deficient medulloblastomas exhibited strikingly distinct pathology, with reduced apoptosis, increased neural differentiation and tectal migration. Comparing Bax(+/+) and Bax(-/-) medulloblastomas, we were able to identify upregulation of Bcl-2 and nuclear exclusion of p27 as tumorigenic changes that are required to mitigate the tumor suppressive effect of Bax. Studies on human tumors confirmed the importance of modulating Bax in medulloblastoma pathogenesis. Our results demonstrate that Bax-dependent apoptosis regulates postnatal cerebellar neurogenesis, suppresses medulloblastoma formation and imposes selective pressure on tumors that form. Functional resistance to Bax-mediated apoptosis, required for medulloblastoma tumorigenesis, may be a tumor-specific vulnerability to be exploited for therapeutic benefit.
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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.