ArticleCancer cell2014
Quiescent sox2(+) cells drive hierarchical growth and relapse in sonic hedgehog subgroup medulloblastoma.
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Article in Cancer cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 200 papers.
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200citing papers in PubMed
12.7field-weighted citation impact, top 1% of its field
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200 citing papers in PubMed, 307 citations in OpenAlex.
- Transcriptional activation of EPHB1 by SOX2 promotes epithelial-mesenchymal transition and metastasis in esophageal squamous cell carcinoma.Clinical & experimental metastasis · 2026Article
- From developmental origins to relapse: molecular and therapeutic insights in medulloblastoma.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026Review
- Identification of the MRTFA/SRF pathway as a critical regulator of quiescence and chemotherapy resistance in cancer.Cancer letters · 2026Article
- CK1α agonists attenuate medulloblastoma stemness and relapse risk.Cell death & disease · 2026Article
- PTEN restrains SHH medulloblastoma growth through cell autonomous and nonautonomous mechanisms.eLife · 2026Article
- Male-biased Yap1-Cd276/B7-H3 axis for immune evasion in medulloblastoma.Cancer cell · 2026Article
- Comparative single cell analysis of wound and cancer identifies the metabolic dialogues between tumor initiating stem cells and macrophages.bioRxiv : the preprint server for biology · 2026Article
- Article
- SOX2 is a dispensable modulator of NUT carcinoma oncogenesis in mice.Life science alliance · 2026Article
- Expression of Epithelial-Mesenchymal Transition-Related Genes in Primary Brain Tumors.Iranian biomedical journal · 2026Article
- A conserved differentiation programme facilitates inhibitory neuron production in the developing mouse and human cerebellum.Development (Cambridge, England) · 2025Article
- Evaluation of the prognostic role of SOX2 as a tumor stem cell marker in odontogenic cysts and tumors: clinical, radiographic and immunohistochemical correlation.BMC oral health · 2025Observational
- Hierarchical regulation of cerebellar neurogenesis by Sin3A-mediated gene repression.bioRxiv : the preprint server for biology · 2025Article
- SOX2 commands LIM homeobox transcription factors in choroid plexus development and tumorigenesis.Neuro-oncology · 2025Article
- Modeling glioma intratumoral heterogeneity with primary human neural stem and progenitor cells.Stem cell reports · 2025Article
- SOX2 drives esophageal squamous carcinoma by reprogramming lipid metabolism and histone acetylation landscape.Nature communications · 2025Article
- Inheritable cell-states shape drug-persister correlations and population dynamics in cancer cells.PLoS computational biology · 2025Article
- A forward genetic screen identifies potassium channel essentiality in SHH medulloblastoma maintenance.Developmental cell · 2025Article
- IGFBP-2 and IGF-II: Key Components of the Neural Stem Cell Niche? Implications for Glioblastoma Pathogenesis.International journal of molecular sciences · 2025Review
- OLIG2 mediates a rare targetable stem cell fate transition in sonic hedgehog medulloblastoma.Nature communications · 2025Article
140 more citing papers are in PubMed but not listed here.
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Authors and funding
28 authors at 8 institutions in 3 countries.
Robert J VannerArthur and Sonia Labatt Brain Tumour Research Centre and Division of Neurosurgery, Hospital for Sick Children (HSC), Toronto, ON M5G 1L7, Canada; Program in Developmental and Stem Cell Biology, HSC, Toronto, ON M5G 1X8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Marc RemkeArthur and Sonia Labatt Brain Tumour Research Centre and Division of Neurosurgery, Hospital for Sick Children (HSC), Toronto, ON M5G 1L7, Canada; Program in Developmental and Stem Cell Biology, HSC, Toronto, ON M5G 1X8, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Marco GalloArthur and Sonia Labatt Brain Tumour Research Centre and Division of Neurosurgery, Hospital for Sick Children (HSC), Toronto, ON M5G 1L7, Canada; Program in Developmental and Stem Cell Biology, HSC, Toronto, ON M5G 1X8, Canada.
Hayden J SelvaduraiArthur and Sonia Labatt Brain Tumour Research Centre and Division of Neurosurgery, Hospital for Sick Children (HSC), Toronto, ON M5G 1L7, Canada; Program in Developmental and Stem Cell Biology, HSC, Toronto, ON M5G 1X8, Canada.
Fiona CoutinhoArthur and Sonia Labatt Brain Tumour Research Centre and Division of Neurosurgery, Hospital for Sick Children (HSC), Toronto, ON M5G 1L7, Canada; Program in Developmental and Stem Cell Biology, HSC, Toronto, ON M5G 1X8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Lilian LeeArthur and Sonia Labatt Brain Tumour Research Centre and Division of Neurosurgery, Hospital for Sick Children (HSC), Toronto, ON M5G 1L7, Canada; Program in Developmental and Stem Cell Biology, HSC, Toronto, ON M5G 1X8, Canada.
Michelle KushidaArthur and Sonia Labatt Brain Tumour Research Centre and Division of Neurosurgery, Hospital for Sick Children (HSC), Toronto, ON M5G 1L7, Canada; Program in Developmental and Stem Cell Biology, HSC, Toronto, ON M5G 1X8, Canada.
Renee HeadArthur and Sonia Labatt Brain Tumour Research Centre and Division of Neurosurgery, Hospital for Sick Children (HSC), Toronto, ON M5G 1L7, Canada; Program in Developmental and Stem Cell Biology, HSC, Toronto, ON M5G 1X8, Canada.
Sorana MorrissyArthur and Sonia Labatt Brain Tumour Research Centre and Division of Neurosurgery, Hospital for Sick Children (HSC), Toronto, ON M5G 1L7, Canada; Program in Developmental and Stem Cell Biology, HSC, Toronto, ON M5G 1X8, Canada.
Xueming ZhuArthur and Sonia Labatt Brain Tumour Research Centre and Division of Neurosurgery, Hospital for Sick Children (HSC), Toronto, ON M5G 1L7, Canada; Program in Developmental and Stem Cell Biology, HSC, Toronto, ON M5G 1X8, Canada.
Tzvi AvivArthur and Sonia Labatt Brain Tumour Research Centre and Division of Neurosurgery, Hospital for Sick Children (HSC), Toronto, ON M5G 1L7, Canada; Program in Developmental and Stem Cell Biology, HSC, Toronto, ON M5G 1X8, Canada.
Veronique VoisinThe Donnelly Centre, University of Toronto, Toronto, ON M5S 1A8, Canada.
Ian D ClarkeArthur and Sonia Labatt Brain Tumour Research Centre and Division of Neurosurgery, Hospital for Sick Children (HSC), Toronto, ON M5G 1L7, Canada; Program in Developmental and Stem Cell Biology, HSC, Toronto, ON M5G 1X8, Canada; OCAD University, Toronto, ON M5T1W1, Canada.
Yisu LiCanada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC VSZ 4S6, Canada.
Andrew J MungallCanada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC VSZ 4S6, Canada.
Richard A MooreCanada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC VSZ 4S6, Canada.
Yussanne MaCanada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC VSZ 4S6, Canada.
Steven J M JonesCanada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC VSZ 4S6, Canada.
Marco A MarraCanada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC VSZ 4S6, Canada.
David MalkinDivision of Hematology/Oncology, HSC, Department of Pediatrics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Paul A NorthcottDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg, Germany.
Marcel KoolDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg, Germany.
Stefan M PfisterDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ) Heidelberg, 69120 Heidelberg, Germany; Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital, 69120 Heidelberg, Germany.
Gary BaderThe Donnelly Centre, University of Toronto, Toronto, ON M5S 1A8, Canada.
Konrad HochedlingerMassachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
Andrey KorshunovDepartment of Neuropathology, University of Heidelberg, 69120 Heidelberg, Germany; Clinical Cooperation Unit Neuropathology, German Cancer Research Centre, DKFZ, 69120 Heidelberg, Germany.
Michael D TaylorArthur and Sonia Labatt Brain Tumour Research Centre and Division of Neurosurgery, Hospital for Sick Children (HSC), Toronto, ON M5G 1L7, Canada; Program in Developmental and Stem Cell Biology, HSC, Toronto, ON M5G 1X8, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Peter B DirksArthur and Sonia Labatt Brain Tumour Research Centre and Division of Neurosurgery, Hospital for Sick Children (HSC), Toronto, ON M5G 1L7, Canada; Program in Developmental and Stem Cell Biology, HSC, Toronto, ON M5G 1X8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: peter.dirks@sickkids.ca.
SickKids Foundation · CABC Cancer Agency · CAHospital for Sick Children · CAUniversity of Toronto · CAGerman Cancer Research Center · DEHeidelberg University · DECanada's Michael Smith Genome Sciences Centre · CAMassachusetts General Hospital · US
Funding
Role of Sox2 in stomach development, regeneration and cancerR01DK096034 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI HOCHEDLINGER, KONRAD · 2012 to 2015
$1.4MHoward Hughes Medical InstituteNIDDK NIH HHS R01 DK096034
Abstract
Functional heterogeneity within tumors presents a significant therapeutic challenge. Here we show that quiescent, therapy-resistant Sox2(+) cells propagate sonic hedgehog subgroup medulloblastoma by a mechanism that mirrors a neurogenic program. Rare Sox2(+) cells produce rapidly cycling doublecortin(+) progenitors that, together with their postmitotic progeny expressing NeuN, comprise tumor bulk. Sox2(+) cells are enriched following anti-mitotic chemotherapy and Smoothened inhibition, creating a reservoir for tumor regrowth. Lineage traces from Sox2(+) cells increase following treatment, suggesting that this population is responsible for relapse. Targeting Sox2(+) cells with the antineoplastic mithramycin abrogated tumor growth. Addressing functional heterogeneity and eliminating Sox2(+) cells presents a promising therapeutic paradigm for treatment of sonic hedgehog subgroup medulloblastoma.
Indexed as
Cell ProliferationAnimalsAntigens, NuclearAntineoplastic AgentsBiomarkers, TumorCell LineageCerebellar NeoplasmsDNA-Binding ProteinsDose-Response Relationship, DrugDoublecortin Domain ProteinsDrug Resistance, NeoplasmGene Expression ProfilingGene Expression Regulation, NeoplasticHedgehog ProteinsMedulloblastomaMiceAntigens, NuclearAntineoplastic AgentsBiomarkers, TumorDNA-Binding ProteinsDoublecortin Domain ProteinsHedgehog ProteinsMicrotubule-Associated ProteinsNerve Tissue ProteinsNeuN protein, mouseneuronal nuclear antigen NeuN, humanNeuropeptidesNuclear ProteinsPatched ReceptorsPlicamycinReceptors, Cell SurfaceReceptors, G-Protein-CoupledSHH protein, humanShh protein, mouseSmoothened ReceptorSMO protein, humanSmo protein, mouseSOX2 protein, humanSox2 protein, mouseSOXB1 Transcription Factors
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