ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
Spinal Myxopapillary Ependymomas Demonstrate a Warburg Phenotype.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 47 citations in OpenAlex.
- A brief history of ependymoma.Neuro-oncology · 2026Review
- Single-nucleus transcriptomics of spinal ependymoma subtypes recognizes intratumoral heterogeneity.Neuro-oncology · 2026Article
- Multi-omics analysis delineates molecular signatures of spinal ependymal tumor.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Metformin Increases the Response of Cholangiocarcinoma Cells to Gemcitabine by Suppressing Pyruvate Kinase M2 to Activate Mitochondrial Apoptosis.Digestive diseases and sciences · 2024Article
- When a dermatopathologist encounters the ultra-rare: A case series of superficial soft tissue/cutaneous myxopapillary ependymomas.Journal of cutaneous pathology · 2024Article
- Pediatric CNS tumors and 2021 WHO classification: what do oncologists need from pathologists?Frontiers in molecular neuroscience · 2024Review
- The biology of ependymomas and emerging novel therapies.Nature reviews. Cancer · 2022Review
- Anaplastic myxopapillary ependymoma: A case report and review of literature.World journal of clinical oncology · 2021Article
- A short review on cross-link between pyruvate kinase (PKM2) and Glioblastoma Multiforme.Metabolic brain disease · 2021Review
- Single-Cell RNA-Seq Reveals Cellular Hierarchies and Impaired Developmental Trajectories in Pediatric Ependymoma.Cancer cell · 2020Article
- MYCN amplification drives an aggressive form of spinal ependymoma.Acta neuropathologica · 2019Article
- Clinicopathologic features of anaplastic myxopapillary ependymomas.Brain pathology (Zurich, Switzerland) · 2019Article
- DNA methylation-based classification of ependymomas in adulthood: implications for diagnosis and treatment.Neuro-oncology · 2018Article
- Heterogeneity within the PF-EPN-B ependymoma subgroup.Acta neuropathologica · 2018Article
- Transcriptomic analysis in pediatric spinal ependymoma reveals distinct molecular signatures.Oncotarget · 2017Article
- Put away your microscopes: the ependymoma molecular era has begun.Current opinion in oncology · 2017Review
- MiR-125a regulates mitochondrial homeostasis through targeting mitofusin 1 to control hypoxic pulmonary vascular remodeling.Journal of molecular medicine (Berlin, Germany) · 2017Article
- Characterization of gliomas: from morphology to molecules.Virchows Archiv : an international journal of pathology · 2017Review
- Treatment implications of posterior fossa ependymoma subgroups.Chinese journal of cancer · 2016Article
- Primary spinal myxopapillary ependymoma in the pediatric population: a study from the Surveillance, Epidemiology, and End Results (SEER) database.Journal of neuro-oncology · 2016Article
Corrections and comments
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Authors and funding
30 authors at 7 institutions in 6 countries.
Funding
Abstract
purposeMyxopapillary ependymoma (MPE) is a distinct histologic variant of ependymoma arising commonly in the spinal cord. Despite an overall favorable prognosis, distant metastases, subarachnoid dissemination, and late recurrences have been reported. Currently, the only effective treatment for MPE is gross-total resection. We characterized the genomic and transcriptional landscape of spinal ependymomas in an effort to delineate the genetic basis of this disease and identify new leads for therapy. EXPERIMENTAL
designGene expression profiling was performed on 35 spinal ependymomas, and copy number profiling was done on an overlapping cohort of 46 spinal ependymomas. Functional validation experiments were performed on tumor lysates consisting of assays measuring pyruvate kinase M activity (PKM), hexokinase activity (HK), and lactate production.
resultsAt a gene expression level, we demonstrate that spinal grade II and MPE are molecularly and biologically distinct. These are supported by specific copy number alterations occurring in each histologic variant. Pathway analysis revealed that MPE are characterized by increased cellular metabolism, associated with upregulation of HIF1α. These findings were validated by Western blot analysis demonstrating increased protein expression of HIF1α, HK2, PDK1, and phosphorylation of PDHE1A. Functional assays were performed on MPE lysates, which demonstrated decreased PKM activity, increased HK activity, and elevated lactate production.
conclusionsOur findings suggest that MPE may be driven by a Warburg metabolic phenotype. The key enzymes promoting the Warburg phenotype: HK2, PKM2, and PDK are targetable by small-molecule inhibitors/activators, and should be considered for evaluation in future clinical trials for MPE.
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