ArticleCell reports2015
Genome-wide CRISPR-Cas9 Screens Reveal Loss of Redundancy between PKMYT1 and WEE1 in Glioblastoma Stem-like Cells.
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Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
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112citing papers in PubMed
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Who cites it
112 citing papers in PubMed, 205 citations in OpenAlex.
- Integrated Genetic Screening Identifies FEN1 as a Selective Vulnerability and Temozolomide Resistance Mediator in Glioblastoma Stem Cells.Cancer research communications · 2026Article
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- Design, Synthesis, Biological Activity Evaluation, and Molecular Docking of 2-Aminopyrimidine-Based PKMYT1 Inhibitors.Biomedicines · 2026Article
- The regulation of protein phosphatase 4 by FBXO42 is required for cancer cell survival.EMBO reports · 2026Article
- PKMYT1 in Cancer: Beyond Cell Cycle Checkpoints to Context-Dependent Therapeutic Vulnerability.Genes, chromosomes & cancer · 2026Review
- Integrative Transcriptomic and Functional Analysis of PKMYT1 Reveals a Potential Therapeutic Target in Chronic Lymphocytic Leukemia.Hematological oncology · 2026Article
- Pervasive phenotypic effects of FBXO42 are promoted by regulation of PP4 phosphatase.The EMBO journal · 2026Article
- Defining treatment-resistant brain cancer: Genetic screening to identify oncogene-driven immunomodulation and therapy resistance.Cancer gene therapy · 2026Review
- Integration of omics data in the diagnosis and therapy of glioblastoma.Brain pathology (Zurich, Switzerland) · 2026Review
- Cellular heterogeneity and therapeutic response profiling of human IDH + glioma stem cell cultures.Scientific reports · 2025Article
- Identification of TTLL8, POTEE, and PKMYT1 as immunogenic cancer-associated antigens and potential immunotherapy targets in ovarian cancer.Oncoimmunology · 2025Article
- WEE1 inhibitors trigger GCN2-mediated activation of the integrated stress response.Nature communications · 2025Article
- WEE1 inhibitors synergise with mRNA translation defects via activation of the kinase GCN2.Nature communications · 2025Article
- Characterization of quiescent subpopulations and proliferative compartments in glioblastoma.bioRxiv : the preprint server for biology · 2025Article
- Exploring PKMYT1 as a potential marker for colorectal cancer progression through bioinformatics analyses and experimental validation.Scientific reports · 2025Article
- Synthetic Lethality-Based Targets and Their Exploration in Tumour Combination Strategies.Journal of cellular and molecular medicine · 2025Review
- Unraveling resistance mechanisms to the novel nucleoside analog RX-3117 in lung cancer: insights into DNA repair, cell cycle dysregulation and targeting PKMYT1 for improved therapy.Journal of experimental & clinical cancer research : CR · 2025Article
- KAT5 regulates neurodevelopmental states associated with G0-like populations in glioblastoma.Nature communications · 2025Article
- Perspectives on cancer therapy-synthetic lethal precision medicine strategies, molecular mechanisms, therapeutic targets and current technical challenges.Cell death discovery · 2025Review
- Myt1 Kinase: An Emerging Cell-Cycle Regulator for Cancer Therapeutics.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
52 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 10 institutions in 4 countries.
Chad M ToledoHuman Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Yu DingHuman Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Pia HoellerbauerHuman Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
Ryan J DavisHuman Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Ryan BasomGenomics and Bioinformatics Shared Resources, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Emily J GirardClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Eunjee LeeDepartment of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Philip CorrinHuman Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Traver HartDepartment of Molecular Genetics, University of Toronto and Donnelly Centre, Toronto, ON M5S3E1, Canada; Canadian Institute for Advanced Research, Toronto, ON M5G1Z8, Canada.
Hamid BolouriHuman Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Jerry DavisonGenomics and Bioinformatics Shared Resources, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Qing ZhangGenomics and Bioinformatics Shared Resources, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Justin HardcastleHuman Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Bruce J AronowDivision of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Christopher L PlaisierInstitute for Systems Biology, Seattle, WA 98109, USA.
Nitin S BaligaInstitute for Systems Biology, Seattle, WA 98109, USA.
Jason MoffatDepartment of Molecular Genetics, University of Toronto and Donnelly Centre, Toronto, ON M5S3E1, Canada; Canadian Institute for Advanced Research, Toronto, ON M5G1Z8, Canada.
Qi LinBrain Tumor Program, Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Xiao-Nan LiBrain Tumor Program, Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Do-Hyun NamInstitute for Refractory Cancer Research, Samsung Medical Center, Seoul 135-710, Korea.
Jeongwu LeeDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44192, USA.
Steven M PollardEdinburgh CRUK Cancer Research Centre and MRC Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh EH16 4UU, UK.
Jun ZhuDepartment of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Jeffery J DelrowGenomics and Bioinformatics Shared Resources, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Bruce E ClurmanHuman Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
James M OlsonClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Electronic address: jolson@fredhutch.org.
Patrick J PaddisonHuman Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA. Electronic address: paddison@fredhutch.org.
Fred Hutch Cancer Center · USBaylor College of Medicine · USCanadian Institute for Advanced Research · CAIcahn School of Medicine at Mount Sinai · USInstitute for Systems Biology · USCincinnati Children's Hospital Medical Center · USCleveland Clinic Lerner College of Medicine · USSamsung Medical Center · KRUniversity of Edinburgh · GBUniversity of Washington · US
Funding
Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Marian Esvelt · 1985 to 2026
$296.4MCORE--VECTOR PRODUCTIONP30DK056465 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI HEIMFELD, SHELLY · 1999 to 2014
$14.9MInterdisciplinary Tranining in Cancer ResearchT32CA080416 · NCI · UNIVERSITY OF WASHINGTON · PI STODDARD, BARRY L. · 1998 to 2023
$9.7MTumor Suppression by the Fbw7 Ubiquitin LigaseR01CA084069 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI CLURMAN, BRUCE E · 2000 to 2015
$5.1MTesting a cancer patient-specific SARS-CoV-2 vaccine in chemotherapy- and radiation-treated pediatric brain tumor mouse modelsR01CA114567 · NCI · SEATTLE CHILDREN'S HOSPITAL · PI OLSON, JAMES M · 2006 to 2023
$4.9MMYC-dependent loss of splicing fidelity in Glioblastoma multiformeR01CA190957 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PADDISON, PATRICK · 2015 to 2019
$2.2MInfant and Toddler Brain TumorsR01CA155360 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI OLSON, JAMES M · 2011 to 2015
$1.8MEvolution of cancer-specific molecular requirements for glioblastoma multiforme (R21CA170722 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PADDISON, PATRICK, ZHU, JUN · 2012 to 2013
$418kCancer Research UK 17368Cancer Research UK 19680NCI NIH HHS CA100735NCI NIH HHS P30 CA015704NCI NIH HHS P30CA15704NCI NIH HHS R01 CA084069NCI NIH HHS R01CA084069-11NCI NIH HHS R01 CA114567NCI NIH HHS R01CA114567NCI NIH HHS R01 CA155360NCI NIH HHS R01CA155360NCI NIH HHS R01 CA190957NCI NIH HHS R01CA190957NCI NIH HHS R21 CA170722NCI NIH HHS R21CA170722NCI NIH HHS T32 CA080416NCI NIH HHS T32CA080416NIDDK NIH HHS P30 DK056465
Abstract
To identify therapeutic targets for glioblastoma (GBM), we performed genome-wide CRISPR-Cas9 knockout (KO) screens in patient-derived GBM stem-like cells (GSCs) and human neural stem/progenitors (NSCs), non-neoplastic stem cell controls, for genes required for their in vitro growth. Surprisingly, the vast majority GSC-lethal hits were found outside of molecular networks commonly altered in GBM and GSCs (e.g., oncogenic drivers). In vitro and in vivo validation of GSC-specific targets revealed several strong hits, including the wee1-like kinase, PKMYT1/Myt1. Mechanistic studies demonstrated that PKMYT1 acts redundantly with WEE1 to inhibit cyclin B-CDK1 activity via CDK1-Y15 phosphorylation and to promote timely completion of mitosis in NSCs. However, in GSCs, this redundancy is lost, most likely as a result of oncogenic signaling, causing GBM-specific lethality.
Indexed as
Genome, HumanCDC2 Protein KinaseCell Cycle ProteinsCell SurvivalCRISPR-Cas SystemsCyclin BErbB ReceptorsGene LibraryGlioblastomaHumansMembrane ProteinsMicroscopy, VideoMitosisNeoplastic Stem CellsNuclear ProteinsPhosphorylationadavosertibCDC2 Protein KinaseCell Cycle ProteinsCyclin BEGFR protein, humanErbB ReceptorsMembrane ProteinsNuclear ProteinsPKMYT1 protein, humanProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene Proteins c-aktPyrazolesPyrimidinesPyrimidinonesTumor Suppressor Protein p53WEE1 protein, humancancer therapeuticsCRISPR-Cas9functional genomicsgene editingGlioblastomaMyt1PKMYT1WEE1
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