ArticleCancer research2017
PTEN Signaling in the Postnatal Perivascular Progenitor Niche Drives Medulloblastoma Formation.
Article in Cancer research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- TheInternational journal of molecular sciences · 2024Article
- Developmental basis of SHH medulloblastoma heterogeneity.Nature communications · 2024Article
- SHH medulloblastoma and very early onset of bowel polyps in a child withFrontiers in molecular neuroscience · 2023Review
- Clinical and Molecular Features in Medulloblastomas Subtypes in Children in a Cohort in Taiwan.Cancers · 2022Article
- Review
- Endothelial-Tumor Cell Interaction in Brain and CNS Malignancies.International journal of molecular sciences · 2020Review
- Medulloblastoma, macrocephaly, and a pathogenic germline PTEN variant: Cause or coincidence?Molecular genetics & genomic medicine · 2020Article
- Modeling pediatric medulloblastoma.Brain pathology (Zurich, Switzerland) · 2020Review
- Molecular-Clinical Correlation in Pediatric Medulloblastoma: A Cohort Series Study of 52 Cases in Taiwan.Cancers · 2020Article
- Recent advances in SHH medulloblastoma progression: tumor suppressor mechanisms and the tumor microenvironment.F1000Research · 2019Review
- Engineering Inducible Knock-In Mice to Model Oncogenic Brain Tumor Mutations from Endogenous Loci.Methods in molecular biology (Clifton, N.J.) · 2019Article
- Reproducibility of academic preclinical translational research: lessons from the development of Hedgehog pathway inhibitors to treat cancer.Open biology · 2018Review
- Tuberous sclerosis complex-associated CNS abnormalities depend on hyperactivation of mTORC1 and Akt.The Journal of clinical investigation · 2018Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Loss of the tumor suppressor gene PTEN exerts diverse outcomes on cancer in different developmental contexts. To gain insight into the effect of its loss on outcomes in the brain, we conditionally inactivated the murine Pten gene in neonatal neural stem/progenitor cells. Pten inactivation created an abnormal perivascular proliferative niche in the cerebellum that persisted in adult animals but did not progress to malignancy. Proliferating cells showed undifferentiated morphology and expressed the progenitor marker Nestin but not Math1, a marker of committed granule neuron progenitors. Codeletion of Pten and Trp53 resulted in fully penetrant medulloblastoma originating from the perivascular niche, which exhibited abnormal blood vessel networks and advanced neuronal differentiation of tumor cells. EdU pulse-chase experiments demonstrated a perivascular cancer stem cell population in Pten/Trp53 double mutant medulloblastomas. Genetic analyses revealed recurrent somatic inactivations of the tumor suppressor gene Ptch1 and a recapitulation of the sonic hedgehog subgroup of human medulloblastomas. Overall, our results showed that PTEN acts to prevent the proliferation of a progenitor niche in postnatal cerebellum predisposed to oncogenic induction of medulloblastoma. Cancer Res; 77(1); 123-33. ©2016 AACR.
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