ArticleNeuro-oncology2014
A novel C19MC amplified cell line links Lin28/let-7 to mTOR signaling in embryonal tumor with multilayered rosettes.
Article in Neuro-oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 64 citations in OpenAlex.
- The emerging role of intraoperative nanopore sequencing on the neurosurgical strategy in paediatric embryonal brain tumours.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026Review
- The future of targeted therapies for pediatric central nervous system tumors.Neuro-oncology advances · 2026Review
- ETMR stem-like state and chemo-resistance are supported by perivascular cells at single-cell resolution.Nature communications · 2025Article
- Cellular hierarchies of embryonal tumors with multilayered rosettes are shaped by oncogenic microRNAs and receptor-ligand interactions.Nature cancer · 2025Article
- Molecular mechanism and therapeutic strategies for embryonal tumors with multilayered rosettes in children (Review).Molecular and clinical oncology · 2025Review
- An Anticancer Bioactive Peptide Combined with Oxaliplatin Inhibited Gastric Cancer CellsCurrent protein & peptide science · 2025Article
- Integrated proteomics spotlight the proteasome as a therapeutic vulnerability in embryonal tumors with multilayered rosettes.Neuro-oncology · 2024Article
- LIN28B and Let-7 in Diffuse Midline Glioma: A Review.Cancers · 2023Review
- Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials.Cancers · 2023Review
- Embryonal tumors with multilayered rosettes,Frontiers in oncology · 2022Article
- C19MC amplification and expression of Lin28A and Olig2 in the classification of embryonal tumors of the central nervous system: A 14-year retrospective study from a tertiary care center.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2021Article
- Delta-24-RGD, an Oncolytic Adenovirus, Increases Survival and Promotes Proinflammatory Immune Landscape Remodeling in Models of AT/RT and CNS-PNET.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Embryonal tumors with multi-layered rosettes: a disease of dysregulated miRNAs.Journal of neuro-oncology · 2020Review
- Article
- ETMR: a tumor entity in its infancy.Acta neuropathologica · 2020Review
- Article
- Patient-Derived Orthotopic Xenograft Models of Pediatric Brain Tumors: In a Mature Phase or Still in Its Infancy?Frontiers in oncology · 2019Review
- High LIN28A and PLK4 co‑expression is associated with poor prognosis in epithelial ovarian cancer.Molecular medicine reports · 2018Article
- Embryonal Tumors of the Central Nervous System in Children: The Era of Targeted Therapeutics.Bioengineering (Basel, Switzerland) · 2018Review
- Molecular Classification and Management of Rare Pediatric Embryonal Brain Tumors.Current oncology reports · 2018Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEmbryonal tumor with multilayered rosettes (ETMR) is an aggressive central nervous system primitive neuroectodermal tumor (CNS-PNET) variant. ETMRs have distinctive histology, amplification of the chromosome 19 microRNA cluster (C19MC) at chr19q13.41-42, expression of the RNA binding protein Lin28, and dismal prognosis. Functional and therapeutic studies of ETMR have been limited by a lack of model systems.
methodsWe have established a first cell line, BT183, from a case of ETMR and characterized its molecular and cellular features. LIN28 knockdown was performed in BT183 to examine the potential role of Lin28 in regulating signaling pathway gene expression in ETMR. Cell line findings were corroborated with immunohistochemical studies in ETMR tissues. A drug screen of 73 compounds was performed to identify potential therapeutic targets.
resultsThe BT183 line maintains C19MC amplification, expresses C19MC-encoded microRNAs, and is tumor initiating. ETMRs, including BT183, have high LIN28 expression and low let-7 miRNA expression, and show evidence of mTOR pathway activation. LIN28 knockdown increases let-7 expression and decreases expression of IGF/PI3K/mTOR pathway components. Pharmacologic inhibition of the mTOR pathway reduces BT183 cell viability.
conclusionsBT183 retains key genetic and histologic features of ETMR. In ETMR, Lin28 is not only a diagnostic marker but also a regulator of genes involved in growth and metabolism. Our findings indicate that inhibitors of the IGF/PI3K/mTOR pathway may be promising novel therapies for these fatal embryonal tumors. As the first patient-derived cell line of these rare tumors, BT183 is an important, unique reagent for investigating ETMR biology and therapeutics.
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