ArticleScience signaling2018
Developmental phosphoproteomics identifies the kinase CK2 as a driver of Hedgehog signaling and a therapeutic target in medulloblastoma.
Article in Science signaling, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 82 citations in OpenAlex.
- LC-MS/MS method for quantitation of the CK2 inhibitor silmitasertib (CX-4945) in human plasma, CSF, and brain tissue, and application to a clinical pharmacokinetic study in children with brain tumors.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2020Trial
- Article
- Switching off CK2-mediated activation of survivin offers new therapeutic opportunities in neuroblastoma.Experimental & molecular medicine · 2026Article
- CSNK2B Mutation: A Rare Cause of IGHD.Clinical endocrinology · 2025Article
- Development of an orthotopic medulloblastoma zebrafish model for rapid drug testing.Neuro-oncology · 2025Article
- Ezh2 Delays Activation of Differentiation Genes During Normal Cerebellar Granule Neuron Development and in Medulloblastoma.bioRxiv : the preprint server for biology · 2024Article
- Identification of tumor rejection antigens and the immunologic landscape of medulloblastoma.Genome medicine · 2024Article
- Mechanistic insights into medulloblastoma relapse.Pharmacology & therapeutics · 2024Review
- Article
- Protein kinase CK2 - diverse roles in cancer cell biology and therapeutic promise.Molecular and cellular biochemistry · 2023Review
- Advances in the Treatment of Pediatric Brain Tumors.Children (Basel, Switzerland) · 2022Review
- Hedgehog signaling mechanism and role in cancer.Seminars in cancer biology · 2022Review
- Medulloblastoma in the Modern Era: Review of Contemporary Trials, Molecular Advances, and Updates in Management.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Multi-omic analysis shows REVEILLE clock genes are involved in carbohydrate metabolism and proteasome function.Plant physiology · 2022Article
- CK2 and the Hallmarks of Cancer.Biomedicines · 2022Review
- Review
- Targeting AKT and CK2 represents a novel therapeutic strategy for SMO constitutive activation-driven medulloblastoma.CNS neuroscience & therapeutics · 2022Article
- Validation of an LC-MS/MS Method for the Quantification of the CK2 Inhibitor Silmitasertib (CX-4945) in Human Plasma.Molecules (Basel, Switzerland) · 2022Article
- Review
- Inhibiting CK2 among Promising Therapeutic Strategies for Gliomas and Several Other Neoplasms.Pharmaceutics · 2022Review
Corrections and comments
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Authors and funding
27 authors at 9 institutions in 3 countries.
Funding
Abstract
A major limitation of targeted cancer therapy is the rapid emergence of drug resistance, which often arises through mutations at or downstream of the drug target or through intrinsic resistance of subpopulations of tumor cells. Medulloblastoma (MB), the most common pediatric brain tumor, is no exception, and MBs that are driven by sonic hedgehog (SHH) signaling are particularly aggressive and drug-resistant. To find new drug targets and therapeutics for MB that may be less susceptible to common resistance mechanisms, we used a developmental phosphoproteomics approach in murine granule neuron precursors (GNPs), the developmental cell of origin of MB. The protein kinase CK2 emerged as a driver of hundreds of phosphorylation events during the proliferative, MB-like stage of GNP growth, including the phosphorylation of three of the eight proteins commonly amplified in MB. CK2 was critical to the stabilization and activity of the transcription factor GLI2, a late downstream effector in SHH signaling. CK2 inhibitors decreased the viability of primary SHH-type MB patient cells in culture and blocked the growth of murine MB tumors that were resistant to currently available Hh inhibitors, thereby extending the survival of tumor-bearing mice. Because of structural interactions, one CK2 inhibitor (CX-4945) inhibited both wild-type and mutant CK2, indicating that this drug may avoid at least one common mode of acquired resistance. These findings suggest that CK2 inhibitors may be effective for treating patients with MB and show how phosphoproteomics may be used to gain insight into developmental biology and pathology.
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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.