ArticleProceedings of the National Academy of Sciences of the United States of America2011
Neurofibromatosis-1 regulates mTOR-mediated astrocyte growth and glioma formation in a TSC/Rheb-independent manner.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
56 citing papers in PubMed, 98 citations in OpenAlex.
- A phase II trial of everolimus, temozolomide, and radiotherapy in patients with newly diagnosed glioblastoma: NCCTG N057K.Neuro-oncology · 2015Trial
- Genetic and non-genetic factors influencing phenotypic variability in neurofibromatosis type 1.Orphanet journal of rare diseases · 2026Review
- Current Perspectives on Pediatric Low-Grade Gliomas: Focus on BRAF and MEK Inhibition.Brain tumor research and treatment · 2026Review
- Molecular-targeted therapy for childhood low-grade glial and glioneuronal tumors.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2024Review
- An Overview of Optic Pathway Glioma With Neurofibromatosis Type 1: Pathogenesis, Risk Factors, and Therapeutic Strategies.Investigative ophthalmology & visual science · 2024Review
- Visual Deficits and Diagnostic and Therapeutic Strategies for Neurofibromatosis Type 1: Bridging Science and Patient-Centered Care.Vision (Basel, Switzerland) · 2024Review
- Pten knockout affects drug resistance differently in melanoma and kidney cancer.Pharmacological reports : PR · 2023Article
- Identification of ligand-receptor pairs that drive human astrocyte development.Nature neuroscience · 2023Article
- Metabolic Rewiring in Adult-Type Diffuse Gliomas.International journal of molecular sciences · 2023Review
- Pediatric low-grade glioma models: advances and ongoing challenges.Frontiers in oncology · 2023Review
- RAS and beyond: the many faces of the neurofibromatosis type 1 protein.Disease models & mechanisms · 2022Article
- Identification of FMRP target mRNAs in the developmental brain: FMRP might coordinate Ras/MAPK, Wnt/β-catenin, and mTOR signaling during corticogenesis.Molecular brain · 2020Article
- Clinical trials using molecular stratification of pediatric brain tumors.Translational pediatrics · 2020Review
- Review
- Molecular Characterization of Primary Human Astrocytes Using Digital Gene Expression Analysis.Korean journal of neurotrauma · 2019Article
- Determination of genetic aberrations and novel transcripts involved in the pathogenesis of oligodendroglioma using array comparative genomic hybridization and next generation sequencing.Oncology letters · 2019Article
- Management of pediatric low-grade glioma.Current opinion in pediatrics · 2019Review
- Subependymal giant cell astrocytoma-like astrocytoma: a neoplasm with a distinct phenotype and frequent neurofibromatosis type-1-association.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2018Article
- Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding of kinase and non-kinase clients.The EMBO journal · 2017Article
- Immunohistochemical Markers for Prospective Studies in Neurofibromatosis-1 Porcine Models.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Converging evidence from the analysis of human brain tumors and genetically engineered mice has revealed that the mammalian target of rapamycin (mTOR) pathway is a central regulator of glial and glioma cell growth. In this regard, mutational inactivation of neurofibromatosis-1 (NF1), tuberous sclerosis complex (TSC), and PTEN genes is associated with glioma formation, such that pharmacologic inhibition of mTOR signaling results in attenuated tumor growth. This shared dependence on mTOR suggests that PTEN and NF1 (neurofibromin) glial growth regulation requires TSC/Rheb (Ras homolog enriched in brain) control of mTOR function. In this report, we use a combination of genetic silencing in vitro and conditional mouse transgenesis approaches in vivo to demonstrate that neurofibromin regulates astrocyte cell growth and glioma formation in a TSC/Rheb-independent fashion. First, we show that Nf1 or Pten inactivation, but not Tsc1 loss or Rheb overexpression, increases astrocyte cell growth in vitro. Second, Nf1-deficient increased mTOR signaling and astrocyte hyperproliferation is unaffected by Rheb shRNA silencing. Third, conditional Tsc1 inactivation or Rheb overexpression in glial progenitors of Nf1(+/-) mice does not lead to glioma formation. Collectively, these findings establish TSC/Rheb-independent mechanisms for mTOR-dependent glial cell growth control and gliomagenesis relevant to the design of therapies for individuals with glioma.
Indexed as
Identifiers
What OpenQuestion holds
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.