ArticleCancer research2022
VRK1 Is a Synthetic-Lethal Target in VRK2-Deficient Glioblastoma.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 65 citations in OpenAlex.
- Structure-guided engineering of an aptamer-PROTAC for targeted degradation of vaccinia-related kinase 1.Chemical science · 2026Article
- Structure-based discovery of selective vaccinia-related kinase 1 inhibitors and fluorogenic active-site probes.The Journal of biological chemistry · 2026Article
- VRK1 Is a Novel Therapeutic Target for Small Cell Neuroendocrine Carcinoma of the Cervix.Cancer science · 2026Article
- Barrier-to-Autointegration Factor 1: a key regulator of nuclear envelope integrity, genome stability, and disease progression.Frontiers in immunology · 2026Review
- Histone Lactylation-Driven Upregulation of VRK1 Expression Promotes Stemness and Proliferation of Glioma Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cancer-Type-Specific DNA Methylation Is a Source of Vulnerability in Liver Cancer Cells.Cancer science · 2025Article
- The synthetic lethal interaction between CDS1 and CDS2 is a vulnerability in uveal melanoma and across multiple tumor types.Nature genetics · 2025Article
- VRK1 promotes epithelial-mesenchymal transition in hepatocellular carcinoma mediated by SNAI1 via phosphorylating CHD1L.Cell death & disease · 2025Article
- LIG1 Is a Synthetic Lethal Target in BRCA1 Mutant Cancers.Molecular cancer therapeutics · 2025Article
- The present and future of the Cancer Dependency Map.Nature reviews. Cancer · 2025Review
- Nuclear functions regulated by the VRK1 kinase.Nucleus (Austin, Tex.) · 2024Review
- Targeting the Sodium-Potassium Pump as a Therapeutic Strategy in Acute Myeloid Leukemia.Cancer research · 2024Article
- Radiogenomic profiling of global DNA methylation associated with molecular phenotypes and immune features in glioma.BMC medicine · 2024Article
- New Horizons of Synthetic Lethality in Cancer: Current Development and Future Perspectives.Journal of medicinal chemistry · 2024Review
- Frequent loss ofiScience · 2024Article
- VRK1 promotes DNA-induced type I interferon production.Molecular biology reports · 2024Article
- Advances in synthetic lethality modalities for glioblastoma multiforme.Open medicine (Warsaw, Poland) · 2024Review
- Article
- Genome-Wide CRISPR Screens Identify Multiple Synthetic Lethal Targets That Enhance KRASG12C Inhibitor Efficacy.Cancer research · 2023Article
- The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase.Epigenetics & chromatin · 2023Article
Corrections and comments
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Authors and funding
25 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synthetic lethality is a genetic interaction that results in cell death when two genetic deficiencies co-occur but not when either deficiency occurs alone, which can be co-opted for cancer therapeutics. Pairs of paralog genes are among the most straightforward potential synthetic-lethal interactions by virtue of their redundant functions. Here, we demonstrate a paralog-based synthetic lethality by targeting vaccinia-related kinase 1 (VRK1) in glioblastoma (GBM) deficient of VRK2, which is silenced by promoter methylation in approximately two thirds of GBM. Genetic knockdown of VRK1 in VRK2-null or VRK2-methylated cells resulted in decreased activity of the downstream substrate barrier to autointegration factor (BAF), a regulator of post-mitotic nuclear envelope formation. Reduced BAF activity following VRK1 knockdown caused nuclear lobulation, blebbing, and micronucleation, which subsequently resulted in G2-M arrest and DNA damage. The VRK1-VRK2 synthetic-lethal interaction was dependent on VRK1 kinase activity and was rescued by ectopic expression of VRK2. In VRK2-methylated GBM cell line-derived xenograft and patient-derived xenograft models, knockdown of VRK1 led to robust tumor growth inhibition. These results indicate that inhibiting VRK1 kinase activity could be a viable therapeutic strategy in VRK2-methylated GBM. SIGNIFICANCE: A paralog synthetic-lethal interaction between VRK1 and VRK2 sensitizes VRK2-methylated glioblastoma to perturbation of VRK1 kinase activity, supporting VRK1 as a drug discovery target in this disease.
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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 Socratic graph.