ArticleNeuro-oncology2024
Integrated proteomics spotlight the proteasome as a therapeutic vulnerability in embryonal tumors with multilayered rosettes.
Article in Neuro-oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 8 citations in OpenAlex.
- The future of targeted therapies for pediatric central nervous system tumors.Neuro-oncology advances · 2026Review
- Integrative proteomics and metabolomics advance early cancer detection and targeted therapy with emerging technologies and clinical applications.Discover oncology · 2026Review
- YAP1::MAML2 fusion, a newly identified genetic anomaly in a posterior fossa infant tumor, associated with the methylation class "embryonal tumor with multilayered rosettes, non-C19MC-altered" in the Heidelberg central nervous system tumor classifier and "embryonal tumor with multilayered rosettes-DICER" in the NIH classifier.Acta neuropathologica communications · 2025Article
- Relevance of proteomics and metabolomics approaches to overview the tumorigenesis and better management of cancer.3 Biotech · 2025Review
- Molecular mechanism and therapeutic strategies for embryonal tumors with multilayered rosettes in children (Review).Molecular and clinical oncology · 2025Review
- LCLAT1 regulates cardiolipin composition, mitochondrial phenotype, Lin28A, and oncogenic signaling networks in ETMR.Neuro-oncology advancesArticle
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundEmbryonal tumors with multilayered rosettes (ETMR) are rare malignant embryonal brain tumors. The prognosis of ETMR is poor and novel therapeutic approaches are desperately needed. Comprehension of ETMR tumor biology is currently based on only few previous molecular studies, which mainly focused on the analyses of nucleic acids. In this study, we explored integrated ETMR proteomics.
methodsUsing mass spectrometry, proteome data were acquired from 16 ETMR and the ETMR cell line BT183. Proteome data were integrated with case-matched global DNA methylation data, publicly available transcriptome data, and proteome data of further embryonal and pediatric brain tumors.
resultsProteome-based cluster analyses grouped ETMR samples according to histomorphology, separating neuropil-rich tumors with neuronal signatures from primitive tumors with signatures relating to stemness and chromosome organization. Integrated proteomics showcased that ETMR and BT183 cells harbor proteasome regulatory proteins in abundance, implicating their strong dependency on the proteasome machinery to safeguard proteostasis. Indeed, in vitro assays using BT183 highlighted that ETMR tumor cells are highly vulnerable toward treatment with the CNS penetrant proteasome inhibitor Marizomib.
conclusionsIn summary, histomorphology stipulates the proteome signatures of ETMR, and proteasome regulatory proteins are pervasively abundant in these tumors. As validated in vitro, proteasome inhibition poses a promising therapeutic option in ETMR.
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