ArticleMolecular cell2021
PRMT6 methylation of RCC1 regulates mitosis, tumorigenicity, and radiation response of glioblastoma stem cells.
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Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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87citing papers in PubMed
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87 citing papers in PubMed, 134 citations in OpenAlex.
- Prmt6 Deficiency or Inhibition Restores Microglial Homeostasis and Promotes Scar-Limited Repair in Adult Spinal Cord Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PRMT6 inhibition or deficiency attenuates diabetic neuropathic pain in male mice and is associated with reduced spinal neuroinflammation, microgliosis, and altered p53-p21 signaling.Journal of neuroinflammation · 2026Article
- PRMT3-Mediated Arginine Methylation Stabilizes PCSK9 to Promote Aortic Valve Calcification.Circulation · 2026Article
- A literature-guided integrative transcriptomic analysis framework for prioritizing angiogenesis-associated genes across cancers.Discover oncology · 2026Article
- An EGFR co-amplified lncRNA HELDR promotes glioblastoma malignancy through KAT7-driven gene programs.Nature cell biology · 2026Article
- Mitophagy-Oxidative Stress Molecular Subtypes Define an Immunosuppressive Ecosystem and Vulnerabilities in Glioblastoma.Journal of cellular and molecular medicine · 2026Article
- PRMT6-mediated EZH2 arginine methylation is critical for breast cancer development.Oncogenesis · 2026Article
- Protein arginine methyltransferases in cancer: mechanisms, functions, and therapeutic opportunities.Journal of biomedical science · 2026Review
- Proteomic landscape analysis of undifferentiated pleomorphic sarcoma.Genome medicine · 2026Article
- Review
- PRMT6 is required for initiating and amplifying macrophage-induced inflammation in heterotopic ossification by increasing CCL2 expression.Bone research · 2026Article
- Dysregulation of post-translational modifications in glioma: advances in pathological mechanisms and clinical targeting strategies.Journal of translational medicine · 2026Review
- Metformin Impairs Breast Cancer Growth through the Inhibition of PRMT6.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PRMT3 Drives IDO1-Dependent Radioresistance and Immunosuppression by Promoting Kynurenine Metabolism in Non-Small Cell Lung Cancer.Cancer research · 2026Article
- Hypoxia-induced PRMT6 expression promotes temozolomide chemoresistance in glioblastoma via G3BP1.Journal of translational medicine · 2026Article
- Targeting c-Myc-p300-CARM1 complex induces ferroptosis and reduces CD8International journal of biological sciences · 2026Article
- Overexpression of key complement regulators in glioblastoma.PloS one · 2026Article
- A single-cell atlas of RNA alternative splicing in the glioma-immune ecosystem.Genome biology · 2025Article
- Endothelial cells-derived SEMA3G suppresses glioblastoma stem cells by inducing c-Myc degradation.Cell death and differentiation · 2025Article
- The Gene Encoding the RCC1 (Regulator of Chromosome Condensation 1) Protein inInternational journal of molecular sciences · 2025Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 6 institutions in 2 countries.
Tianzhi HuangThe Ken & Ruth Davee Department of Neurology, The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Simpson Querrey Institute for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Yongyong YangThe Ken & Ruth Davee Department of Neurology, The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Simpson Querrey Institute for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Xiao SongThe Ken & Ruth Davee Department of Neurology, The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Simpson Querrey Institute for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Xuechao WanThe Ken & Ruth Davee Department of Neurology, The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Simpson Querrey Institute for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Bingli WuThe Ken & Ruth Davee Department of Neurology, The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Simpson Querrey Institute for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Namratha SastryThe Ken & Ruth Davee Department of Neurology, The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Simpson Querrey Institute for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Craig M HorbinskiDepartment of Pathology, The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Department of Neurological Surgery, The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Chang ZengDepartment of Preventive Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Deanna TiekThe Ken & Ruth Davee Department of Neurology, The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Simpson Querrey Institute for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Anshika GoenkaThe Ken & Ruth Davee Department of Neurology, The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Simpson Querrey Institute for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Fabao LiuMcArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
Cameron W BrennanHuman Oncology and Pathogenesis Program, Department of Neurosurgery, Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
John A KesslerThe Ken & Ruth Davee Department of Neurology, The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Simpson Querrey Institute for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Roger StuppThe Ken & Ruth Davee Department of Neurology, The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Simpson Querrey Institute for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Department of Neurological Surgery, The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Ichiro NakanoDepartment of Neurosurgery, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Erik P SulmanDepartment of Radiation Oncology, New York University Grossman School of Medicine, New York, NY 10016, USA.
Ryo NishikawaDepartment of Neuro-Oncology/Neurosurgery, Saitama Medical University International Medical Center, Saitama 350-1298, Japan.
Charles David JamesDepartment of Neurological Surgery, The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Wei ZhangDepartment of Preventive Medicine, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Wei XuMcArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
Bo HuThe Ken & Ruth Davee Department of Neurology, The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Simpson Querrey Institute for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address: bo.hu@northwestern.edu.
Shi-Yuan ChengThe Ken & Ruth Davee Department of Neurology, The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Simpson Querrey Institute for Epigenetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address: shiyuan.cheng@northwestern.edu.
Northwestern University · USUniversity of Wisconsin–Madison · USMemorial Sloan Kettering Cancer Center · USNew York University · USSaitama Medical University · JPUniversity of Alabama at Birmingham · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MTumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9MNorthwestern University Clinical and Translational Science Institute (NUCATS)UL1TR001422 · NCATS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI D'AQUILA, RICHARD · 2015 to 2023
$56.8MSTINGing GBM: A First-in- Man Clinical Trial in Surgical Resectable Recurrent GBMP50CA221747 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Pouya Jamshidi · 2018 to 2026
$21.4MThe unique roles of the GTP-binding/protein crosslinking enzyme transglutaminase-2 and signaling partners in aggressive cancersR01CA201402 · NCI · CORNELL UNIVERSITY · PI CERIONE, RICHARD A. · 2016 to 2024
$4.3MProtein Arginine Methylation in Breast CancerR01CA236356 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Wei Xu · 2019 to 2026
$2.9MRole of Protein Methylation in Cell Mitosis and GlioblastomaR01NS115403 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI CHENG, SHI-YUAN · 2020 to 2024
$2.1MRole of BMP Signaling in the Aging Brain R01 AG054429R01AG054429 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI KESSLER, JOHN A · 2017 to 2021
$1.9MGlioblastoma Phenotype Modulation Through miRNA Control of Wnt SignalingR01NS093843 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI CHENG, SHI-YUAN · 2015 to 2019
$1.8MTissue Factor as a Key Determinant of IDH1 Mutant versus IDH1 Wild-type Glioma Thrombosis and MalignancyR01NS102669 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI HORBINSKI, CRAIG MICHAEL · 2017 to 2021
$1.7MAutophagy Regulation of Glioblastoma Tumorigenesis and Responses to TherapyR01NS095634 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI CHENG, SHI-YUAN · 2015 to 2019
$1.7MRadiation + Temozolomide Induced Mutation and Malignant Progression of GBMR01NS095642 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI JAMES, CHARLES DAVID · 2016 to 2020
$1.6MNCATS NIH HHS UL1 TR001422NCI NIH HHS F31 CA232630NCI NIH HHS K00 CA234799NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA060553NCI NIH HHS P50 CA221747NCI NIH HHS R01 CA201402NCI NIH HHS R01 CA213293NCI NIH HHS R01 CA236356NCI NIH HHS R21 CA209345NIA NIH HHS R01 AG054429NINDS NIH HHS R01 NS093843NINDS NIH HHS R01 NS095634NINDS NIH HHS R01 NS095642NINDS NIH HHS R01 NS102669NINDS NIH HHS R01 NS107071NINDS NIH HHS R01 NS115403NINDS NIH HHS R01 NS117104
Abstract
Aberrant cell proliferation is a hallmark of cancer, including glioblastoma (GBM). Here we report that protein arginine methyltransferase (PRMT) 6 activity is required for the proliferation, stem-like properties, and tumorigenicity of glioblastoma stem cells (GSCs), a subpopulation in GBM critical for malignancy. We identified a casein kinase 2 (CK2)-PRMT6-regulator of chromatin condensation 1 (RCC1) signaling axis whose activity is an important contributor to the stem-like properties and tumor biology of GSCs. CK2 phosphorylates and stabilizes PRMT6 through deubiquitylation, which promotes PRMT6 methylation of RCC1, which in turn is required for RCC1 association with chromatin and activation of RAN. Disruption of this pathway results in defects in mitosis. EPZ020411, a specific small-molecule inhibitor for PRMT6, suppresses RCC1 arginine methylation and improves the cytotoxic activity of radiotherapy against GSC brain tumor xenografts. This study identifies a CK2α-PRMT6-RCC1 signaling axis that can be therapeutically targeted in the treatment of GBM.
Indexed as
Brain NeoplasmsCarcinogenesisCell Cycle ProteinsGlioblastomaGuanine Nucleotide Exchange FactorsNeoplasm ProteinsNuclear ProteinsProtein-Arginine N-MethyltransferasesAnimalsCasein Kinase IICell Line, TumorFemaleHEK293 CellsHumansMaleMiceCasein Kinase IICell Cycle ProteinsGuanine Nucleotide Exchange FactorsNeoplasm ProteinsNuclear ProteinsPRMT6 protein, humanProtein-Arginine N-MethyltransferasesRCC1 protein, humanarginine methylationCK2GBMGSCmitosisphosphorylationPRMTRCC1therapy responsetumorigenicity
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