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

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 tha...

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Autores principales: Annibali, Daniela, Whitfield, Jonathan R., Favuzzi, Emilia, Jauset, Toni, Serrano, Erika, Cuartas, Isabel, Redondo-Campos, Sara, Folch, Gerard, Gonzàlez-Juncà, Alba, Sodir, Nicole M., Massó-Vallés, Daniel, Beaulieu, Marie-Eve, Swigart, Lamorna B., Mc Gee, Margaret M., Somma, Maria Patrizia, Nasi, Sergio, Seoane, Joan, Evan, Gerard I., Soucek, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143920/
https://www.ncbi.nlm.nih.gov/pubmed/25130259
http://dx.doi.org/10.1038/ncomms5632
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author Annibali, Daniela
Whitfield, Jonathan R.
Favuzzi, Emilia
Jauset, Toni
Serrano, Erika
Cuartas, Isabel
Redondo-Campos, Sara
Folch, Gerard
Gonzàlez-Juncà, Alba
Sodir, Nicole M.
Massó-Vallés, Daniel
Beaulieu, Marie-Eve
Swigart, Lamorna B.
Mc Gee, Margaret M.
Somma, Maria Patrizia
Nasi, Sergio
Seoane, Joan
Evan, Gerard I.
Soucek, Laura
author_facet Annibali, Daniela
Whitfield, Jonathan R.
Favuzzi, Emilia
Jauset, Toni
Serrano, Erika
Cuartas, Isabel
Redondo-Campos, Sara
Folch, Gerard
Gonzàlez-Juncà, Alba
Sodir, Nicole M.
Massó-Vallés, Daniel
Beaulieu, Marie-Eve
Swigart, Lamorna B.
Mc Gee, Margaret M.
Somma, Maria Patrizia
Nasi, Sergio
Seoane, Joan
Evan, Gerard I.
Soucek, Laura
author_sort Annibali, Daniela
collection PubMed
description 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.
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spelling pubmed-41439202014-09-03 Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis Annibali, Daniela Whitfield, Jonathan R. Favuzzi, Emilia Jauset, Toni Serrano, Erika Cuartas, Isabel Redondo-Campos, Sara Folch, Gerard Gonzàlez-Juncà, Alba Sodir, Nicole M. Massó-Vallés, Daniel Beaulieu, Marie-Eve Swigart, Lamorna B. Mc Gee, Margaret M. Somma, Maria Patrizia Nasi, Sergio Seoane, Joan Evan, Gerard I. Soucek, Laura Nat Commun Article 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. Nature Pub. Group 2014-08-18 /pmc/articles/PMC4143920/ /pubmed/25130259 http://dx.doi.org/10.1038/ncomms5632 Text en Copyright © 2014, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Article
Annibali, Daniela
Whitfield, Jonathan R.
Favuzzi, Emilia
Jauset, Toni
Serrano, Erika
Cuartas, Isabel
Redondo-Campos, Sara
Folch, Gerard
Gonzàlez-Juncà, Alba
Sodir, Nicole M.
Massó-Vallés, Daniel
Beaulieu, Marie-Eve
Swigart, Lamorna B.
Mc Gee, Margaret M.
Somma, Maria Patrizia
Nasi, Sergio
Seoane, Joan
Evan, Gerard I.
Soucek, Laura
Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis
title Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis
title_full Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis
title_fullStr Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis
title_full_unstemmed Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis
title_short Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis
title_sort myc inhibition is effective against glioma and reveals a role for myc in proficient mitosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143920/
https://www.ncbi.nlm.nih.gov/pubmed/25130259
http://dx.doi.org/10.1038/ncomms5632
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