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Wnt activation as a therapeutic strategy in medulloblastoma.
Manoranjan, Branavan; Venugopal, Chitra; Bakhshinyan, David; Adile, Ashley A; Richards, Laura; Kameda-Smith, Michelle M; Whitley, Owen; Dvorkin-Gheva, Anna; Subapanditha, Minomi; Savage, Neil; Tatari, Nazanin; McKenna, Dillon; Bassey-Archibong, Blessing; Winegarden, Neil; Hallett, Robin; Provias, John P; Yarascavitch, Blake; Ajani, Olufemi; Fleming, Adam; Bader, Gary D; Pugh, Trevor J; Doble, Bradley W; Singh, Sheila K.
Afiliação
  • Manoranjan B; Section of Neurosurgery, Department of Clinical Neurosciences, University of Calgary, Calgary, AB, T2N 1N4, Canada.
  • Venugopal C; McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada.
  • Bakhshinyan D; Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, McMaster University, Hamilton, ON, L8N 3Z5, Canada.
  • Adile AA; McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada.
  • Richards L; Department of Surgery, Faculty of Health Sciences, McMaster University, Hamilton, ON, L8N 3Z5, Canada.
  • Kameda-Smith MM; McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada.
  • Whitley O; Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, McMaster University, Hamilton, ON, L8N 3Z5, Canada.
  • Dvorkin-Gheva A; McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada.
  • Subapanditha M; Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, McMaster University, Hamilton, ON, L8N 3Z5, Canada.
  • Savage N; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G 2M9, Canada.
  • Tatari N; Department of Medical Biophysics, University of Toronto, Toronto, ON, M5S 1A8, Canada.
  • McKenna D; McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada.
  • Bassey-Archibong B; Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, McMaster University, Hamilton, ON, L8N 3Z5, Canada.
  • Winegarden N; Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.
  • Hallett R; Department of Computer Science, University of Toronto, Toronto, ON, M5S 1A8, Canada.
  • Provias JP; Department of Pathology, Faculty of Health Sciences, McMaster University, Hamilton, ON, L8N 3Z5, Canada.
  • Yarascavitch B; McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada.
  • Ajani O; McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada.
  • Fleming A; McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada.
  • Bader GD; McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada.
  • Pugh TJ; Department of Surgery, Faculty of Health Sciences, McMaster University, Hamilton, ON, L8N 3Z5, Canada.
  • Doble BW; McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada.
  • Singh SK; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G 2M9, Canada.
Nat Commun ; 11(1): 4323, 2020 08 28.
Article em En | MEDLINE | ID: mdl-32859895
ABSTRACT
Medulloblastoma (MB) is defined by four molecular subgroups (Wnt, Shh, Group 3, Group 4) with Wnt MB having the most favorable prognosis. Since prior reports have illustrated the antitumorigenic role of Wnt activation in Shh MB, we aimed to assess the effects of activated canonical Wnt signaling in Group 3 and 4 MBs. By using primary patient-derived MB brain tumor-initiating cell (BTIC) lines, we characterize differences in the tumor-initiating capacity of Wnt, Group 3, and Group 4 MB. With single cell RNA-seq technology, we demonstrate the presence of rare Wnt-active cells in non-Wnt MBs, which functionally retain the impaired tumorigenic potential of Wnt MB. In treating MB xenografts with a Wnt agonist, we provide a rational therapeutic option in which the protective effects of Wnt-driven MBs may be augmented in Group 3 and 4 MB and thereby support emerging data for a context-dependent tumor suppressive role for Wnt/ß-catenin signaling.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Cerebelares / Proteínas Wnt / Meduloblastoma Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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XML
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Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Cerebelares / Proteínas Wnt / Meduloblastoma Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article