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

Nature Communications; 5,
Article number:: 4632; doi:10.1038/ncomms5632

Received: 18 February 2014
Accepted: 09 July 2014
Published: 18 August 2014

Abstract

Gliomas are the most common primary tumours affecting the adult central nervous system and respond poorly to standard therapy. is causally implicated in most human tumours and the majority of glioblastomas have elevated levels. Using the dominant negative Omomyc, we previously showed that inhibition is a promising strategy for cancer therapy. Here, we preclinically validate 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 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 in the proficient division of glioma cells.