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

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-Vallés, Marie-Eve Beaulieu, Lamorna B. Swigart, Margaret M. Mc Gee, Maria Patrizia Somma, Sergio Nasi, Joan Seoane, Gerard I. Evan and Laura Soucek ()
Additional contact information
Daniela Annibali: Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco
Jonathan R. Whitfield: Vall d’Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d’Hebron
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
Erika Serrano: Vall d’Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d’Hebron
Isabel Cuartas: Vall d’Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d’Hebron
Sara Redondo-Campos: Vall d’Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d’Hebron
Gerard Folch: Vall d’Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d’Hebron
Alba Gonzàlez-Juncà: Vall d’Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d’Hebron
Nicole M. Sodir: Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco
Daniel Massó-Vallés: Vall d’Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d’Hebron
Marie-Eve Beaulieu: Vall d’Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d’Hebron
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
Gerard I. Evan: Sanger Building, University of Cambridge
Laura Soucek: Vall d’Hebron Institute of Oncology (VHIO), Edifici Mediterrània, Hospital Vall d’Hebron

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms5632

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