ArticleCell cycle (Georgetown, Tex.)2014
Druggable glycolytic requirement for Hedgehog-dependent neuronal and medulloblastoma growth.
Article in Cell cycle (Georgetown, Tex.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- Multi-omics integration and machine learning identify an ACKR1Clinical and translational medicine · 2026Article
- Ldha Regulates Osteosarcoma Lung Metastasis through Hedgehog Signaling.Cancer research communications · 2026Article
- 7,7"-dimethoxyagastisflavone induced MYCN/MYBL2-dependent apoptosis and metabolism reprogramming in Sonic Hedgehog medulloblastoma.Journal of translational medicine · 2026Article
- Metabolic reprogramming and immunosenescence: a new sight for glioma therapy.Frontiers in cell and developmental biology · 2026Review
- Hedgehog pathway, cell cycle, and primary cilium.Cell death discovery · 2025Review
- Hedgehog pathway and cancer: A new area (Review).Oncology reports · 2024Review
- SALL4 is a CRL3Cell death and differentiation · 2024Article
- Research progress in molecular pathology markers in medulloblastoma.Exploration of targeted anti-tumor therapy · 2023Review
- Hedgehog signaling can enhance glycolytic ATP production in the Drosophila wing disc.EMBO reports · 2022Article
- Redox-Regulation in Cancer Stem Cells.Biomedicines · 2022Review
- Targeting AKT and CK2 represents a novel therapeutic strategy for SMO constitutive activation-driven medulloblastoma.CNS neuroscience & therapeutics · 2022Article
- Glycolytic Metabolic Remodeling by the Truncate of Glioma-Associated Oncogene Homolog 1 in Triple-Negative Breast Cancer Cells.Journal of Cancer · 2022Article
- Pathological implications of metabolic reprogramming and its therapeutic potential in medulloblastoma.Frontiers in cell and developmental biology · 2022Review
- A short review on cross-link between pyruvate kinase (PKM2) and Glioblastoma Multiforme.Metabolic brain disease · 2021Review
- Biological Role of MYCN in Medulloblastoma: Novel Therapeutic Opportunities and Challenges Ahead.Frontiers in oncology · 2021Review
- Blockade of EIF5A hypusination limits colorectal cancer growth by inhibiting MYC elongation.Cell death & disease · 2020Article
- Review
- Review
- Differential Expression of Mitochondrial Biogenesis Markers in Mouse and Human SHH-Subtype Medulloblastoma.Cells · 2019Article
- Polyamine Metabolism as a Therapeutic Target inHedgehog-Driven Basal Cell Carcinomaand Medulloblastoma.Cells · 2019Review
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant activation of SHH pathway is a major cause of medulloblastoma (MB), the most frequent brain malignancy of the childhood. A few Hedgehog inhibitors, all antagonizing the membrane transducer Smo, have been approved or are under clinical trials for the treatment of human MB. However, the efficacy of these drugs is limited by the occurrence of novel mutations or by activation of downstream or non-canonical Hedgehog components. Thus, the identification of novel druggable downstream pathways represents a critical step to overcome this problem. In the present work we demonstrate that aerobic glycolysis is a valuable HH-dependent downstream target, since its inhibition significantly counteracts the HH-mediated growth of normal and tumor cells. Hedgehog activation induces transcription of hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2), two key gatekeepers of glycolysis. The process is mediated by the canonical activation of the Gli transcription factors and causes a robust increase of extracellular lactate concentration. We show that inhibition of glycolysis at different levels blocks the Hedgehog-induced proliferation of granule cell progenitors (GCPs), the cells from which medulloblastoma arises. Remarkably, we demonstrate that this glycolytic transcriptional program is also upregulated in SHH-dependent tumors and that pharmacological targeting with the pyruvate kinase inhibitor dichloroacetate (DCA) efficiently represses MB growth in vitro and in vivo. Together, these data illustrate a previously uncharacterized pharmacological strategy to target Hedgehog dependent growth, which can be exploited for the treatment of medulloblastoma patients.
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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.