TY - JOUR
T1 - Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis
AU - Annibali, Daniela
AU - Whitfield, Jonathan R.
AU - Favuzzi, Emilia
AU - Jauset, Toni
AU - Serrano, Erika
AU - Cuartas, Isabel
AU - Redondo-Campos, Sara
AU - Folch, Gerard
AU - Gonzàlez-Juncà, Alba
AU - Sodir, Nicole M.
AU - Massó-Vallés, Daniel
AU - Beaulieu, Marie Eve
AU - Swigart, Lamorna B.
AU - Mc Gee, Margaret M.
AU - Somma, Maria Patrizia
AU - Nasi, Sergio
AU - Seoane, Joan
AU - Evan, Gerard I.
AU - Soucek, Laura
PY - 2014/8/18
Y1 - 2014/8/18
N2 - 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.
AB - 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.
U2 - https://doi.org/10.1038/ncomms5632
DO - https://doi.org/10.1038/ncomms5632
M3 - Article
VL - 5
M1 - 4632
ER -