ArticleOncotarget2014
Vaccinia-related kinase 1 (VRK1) confers resistance to DNA-damaging agents in human breast cancer by affecting DNA damage response.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 74 citations in OpenAlex.
- Epigenetic Factor Dysregulation and Distinct Expression Signatures in Retinoblastoma: A Transcriptomic Analysis.Investigative ophthalmology & visual science · 2026Article
- Breast cancer genomic subtype-specific copy number alterations in metastases.Scientific reports · 2026Article
- Nuclear functions regulated by the VRK1 kinase.Nucleus (Austin, Tex.) · 2024Review
- Pathogenic effects of Leu200Pro and Arg387His VRK1 protein variants on phosphorylation targets and H4K16 acetylation in distal hereditary motor neuropathy.Journal of molecular medicine (Berlin, Germany) · 2024Article
- The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase.Epigenetics & chromatin · 2023Article
- VRK1 Kinase Activity Modulating Histone H4K16 Acetylation Inhibited by SIRT2 and VRK-IN-1.International journal of molecular sciences · 2023Article
- Integrative multi-omics networks identify PKCδ and DNA-PK as master kinases of glioblastoma subtypes and guide targeted cancer therapy.Nature cancer · 2023Article
- Targeting Histone Epigenetic Modifications and DNA Damage Responses in Synthetic Lethality Strategies in Cancer?Cancers · 2022Article
- DNA Aptamers against Vaccinia-Related Kinase (VRK) 1 Block Proliferation in MCF7 Breast Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Lysine Methyltransferase Inhibitors Impair H4K20me2 and 53BP1 Foci in Response to DNA Damage in Sarcomas, a Synthetic Lethality Strategy.Frontiers in cell and developmental biology · 2021Article
- VRK1 Depletion Facilitates the Synthetic Lethality of Temozolomide and Olaparib in Glioblastoma Cells.Frontiers in cell and developmental biology · 2021Article
- Identification of VRK1 as a New Neuroblastoma Tumor Progression Marker Regulating Cell Proliferation.Cancers · 2020Article
- VRK1 Phosphorylates Tip60/KAT5 and Is Required for H4K16 Acetylation in Response to DNA Damage.Cancers · 2020Article
- Microarray data analysis reveals gene expression changes in response to ionizing radiation in MCF7 human breast cancer cells.Hereditas · 2020Article
- Downregulation of VRK1 reduces the expression of BANF1 and suppresses the proliferative and migratory activity of esophageal cancer cells.Oncology letters · 2020Article
- VRK1 functional insufficiency due to alterations in protein stability or kinase activity of human VRK1 pathogenic variants implicated in neuromotor syndromes.Scientific reports · 2019Article
- 4-Hydroxytamoxifen enhances sensitivity of estrogen receptor α-positive breast cancer to docetaxel in an estrogen and ZNF423 SNP-dependent fashion.Breast cancer research and treatment · 2019Article
- Olaparib and ionizing radiation trigger a cooperative DNA-damage repair response that is impaired by depletion of the VRK1 chromatin kinase.Journal of experimental & clinical cancer research : CR · 2019Article
- A novel mutation in VRK1 associated with distal spinal muscular atrophy.Journal of human genetics · 2019Article
- Crystal structure of human vaccinia-related kinase 1 in complex with AMP-PNP, a non-hydrolyzable ATP analog.Protein science : a publication of the Protein Society · 2019Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vaccinia-related kinase 1 (VRK1) belongs to a group of sixteen kinases associated to a poorer prognosis in human breast carcinomas, particularly in estrogen receptor positive cases based on gene expression arrays. In this work we have studied the potential molecular mechanism by which the VRK1 protein can contribute to a poorer prognosis in this disease. For this aim it was first analyzed by immunohistochemistry the VRK1 protein level in normal breast and in one hundred and thirty six cases of human breast cancer. The effect of VRK1 to protect against DNA damage was determined by studying the effect of its knockdown on the formation of DNA repair foci assembled on 53BP1 in response to treatment with ionizing radiation or doxorubicin in two breast cancer cell lines. VRK1 protein was detected in normal breast and in breast carcinomas at high levels in ER and PR positive tumors. VRK1 protein level was significantly lower in ERBB2 positive cases. Next, to identify a mechanism that can link VRK1 to poorer prognosis, VRK1 was knocked-down in two breast cancer cell lines that were treated with ionizing radiation or doxorubicin, both inducing DNA damage. Loss of VRK1 resulted in reduced formation of DNA-damage repair foci complexes assembled on the 53BP1 scaffold protein, and this effect was independent of damaging agent or cell type. This observation is consistent with detection of high VRK1 protein levels in ER and PR positive breast cancers. We conclude that VRK1 can contribute to make these tumors more resistant to DNA damage-based therapies, such as ionizing radiation or doxorubicin, which is consistent with its association to a poor prognosis in ER positive breast cancer. VRK1 is potential target kinase for development of new specific inhibitors which can facilitate sensitization to other treatments in combination therapies; or alternatively be used as a new cancer drugs.
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