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, Laura Soucek

Research output: Contribution to journalArticleResearchpeer-review

84 Citations (Scopus)

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. © 2014 Macmillan Publishers Limited. All rights reserved.
Original languageEnglish
Article number4632
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 18 Aug 2014

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