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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Annibali, Daniela 
Whitfield, Jonathan R 
Favuzzi, Emilia 
Jauset, Toni 
Serrano, Erika 

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.

Description

Keywords

Animals, Apoptosis, Astrocytoma, Brain Neoplasms, Cell Line, Tumor, Cell Proliferation, Disease Models, Animal, Glioblastoma, Glioma, Heterografts, Humans, Mice, Mice, Transgenic, Mitosis, Protein Tyrosine Phosphatase, Non-Receptor Type 1, Proto-Oncogene Proteins c-myc, Ubiquitin-Activating Enzymes

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

5

Publisher

Springer Science and Business Media LLC
Sponsorship
Cancer Research Uk (None)
Cancer Research Uk (None)