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Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis

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  • Daniela Annibali

    (Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco
    Istituto di Biologia, Medicina Molecolare e NanoBiotecnologie, C.N.R., Università La Sapienza)

  • Jonathan R. Whitfield

    (Vall d’Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d’Hebron
    Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès))

  • Emilia Favuzzi

    (Istituto di Biologia, Medicina Molecolare e NanoBiotecnologie, C.N.R., Università La Sapienza)

  • Toni Jauset

    (Vall d’Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d’Hebron
    Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès))

  • Erika Serrano

    (Vall d’Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d’Hebron
    Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès))

  • Isabel Cuartas

    (Vall d’Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d’Hebron
    Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès))

  • Sara Redondo-Campos

    (Vall d’Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d’Hebron
    Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès))

  • Gerard Folch

    (Vall d’Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d’Hebron
    Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès))

  • Alba Gonzàlez-Juncà

    (Vall d’Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d’Hebron
    Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès))

  • Nicole M. Sodir

    (Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco
    Sanger Building, University of Cambridge)

  • Daniel Massó-Vallés

    (Vall d’Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d’Hebron
    Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès))

  • Marie-Eve Beaulieu

    (Vall d’Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d’Hebron
    Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès))

  • Lamorna B. Swigart

    (Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco)

  • Margaret M. Mc Gee

    (UCD School of Biomolecular & Biomedical Science, UCD Conway Institute, University College Dublin)

  • Maria Patrizia Somma

    (Istituto di Biologia, Medicina Molecolare e NanoBiotecnologie, C.N.R., Università La Sapienza)

  • Sergio Nasi

    (Istituto di Biologia, Medicina Molecolare e NanoBiotecnologie, C.N.R., Università La Sapienza)

  • Joan Seoane

    (Vall d’Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d’Hebron
    Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès)
    Institució Catalana de Recerca i Estudis Avançats (ICREA))

  • Gerard I. Evan

    (Sanger Building, University of Cambridge)

  • Laura Soucek

    (Vall d’Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d’Hebron
    Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès))

Abstract

Gliomas are the most common primary tumours affecting the adult central nervous system and respond poorly to standard therapy. Myc is causally implicated in most human tumours and the majority of glioblastomas have elevated Myc levels. Using the Myc dominant negative Omomyc, we previously showed that Myc inhibition is a promising strategy for cancer therapy. Here, we preclinically validate Myc inhibition as a therapeutic strategy in mouse and human glioma, using a mouse model of spontaneous multifocal invasive astrocytoma and its derived neuroprogenitors, human glioblastoma cell lines, and patient-derived tumours both in vitro and in orthotopic xenografts. Across all these experimental models we find that Myc inhibition reduces proliferation, increases apoptosis and remarkably, elicits the formation of multinucleated cells that then arrest or die by mitotic catastrophe, revealing a new role for Myc in the proficient division of glioma cells.

Suggested Citation

  • Daniela Annibali & Jonathan R. Whitfield & Emilia Favuzzi & Toni Jauset & Erika Serrano & Isabel Cuartas & Sara Redondo-Campos & Gerard Folch & Alba Gonzàlez-Juncà & Nicole M. Sodir & Daniel Massó-Val, 2014. "Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5632
    DOI: 10.1038/ncomms5632
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