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Abrogation of Rb Tumor Suppression Initiates GBM in Differentiated Astrocytes by Driving a Progenitor Cell Program

Glioblastoma (GBM) remains lethal with no effective treatments. Despite the comprehensive identification of commonly perturbed molecular pathways, little is known about the disease’s etiology, particularly in early stages. Several studies indicate that GBM is initiated in neural progenitor and/or st...

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Autores principales: Adhikari, Amit S., Sullivan, Teresa, Bargaje, Rhishikesh, Lu, Lucy, O’Sullivan, T Norene, Song, Yurong, Van Dyke, Terry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263358/
https://www.ncbi.nlm.nih.gov/pubmed/35814428
http://dx.doi.org/10.3389/fonc.2022.904479
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author Adhikari, Amit S.
Sullivan, Teresa
Bargaje, Rhishikesh
Lu, Lucy
O’Sullivan, T Norene
Song, Yurong
Van Dyke, Terry
author_facet Adhikari, Amit S.
Sullivan, Teresa
Bargaje, Rhishikesh
Lu, Lucy
O’Sullivan, T Norene
Song, Yurong
Van Dyke, Terry
author_sort Adhikari, Amit S.
collection PubMed
description Glioblastoma (GBM) remains lethal with no effective treatments. Despite the comprehensive identification of commonly perturbed molecular pathways, little is known about the disease’s etiology, particularly in early stages. Several studies indicate that GBM is initiated in neural progenitor and/or stem cells. Here, we report that differentiated astrocytes are susceptible to GBM development when initiated by perturbation of the RB pathway, which induces a progenitor phenotype. In vitro and in vivo inactivation of Rb tumor suppression (TS) induces cortical astrocytes to proliferate rapidly, express progenitor markers, repress differentiation markers, and form self-renewing neurospheres that are susceptible to multi-lineage differentiation. This phenotype is sufficient to cause grade II astrocytomas which stochastically progress to GBM. Together with previous findings, these results demonstrate that cell susceptibility to GBM depends on the initiating driver.
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spelling pubmed-92633582022-07-09 Abrogation of Rb Tumor Suppression Initiates GBM in Differentiated Astrocytes by Driving a Progenitor Cell Program Adhikari, Amit S. Sullivan, Teresa Bargaje, Rhishikesh Lu, Lucy O’Sullivan, T Norene Song, Yurong Van Dyke, Terry Front Oncol Oncology Glioblastoma (GBM) remains lethal with no effective treatments. Despite the comprehensive identification of commonly perturbed molecular pathways, little is known about the disease’s etiology, particularly in early stages. Several studies indicate that GBM is initiated in neural progenitor and/or stem cells. Here, we report that differentiated astrocytes are susceptible to GBM development when initiated by perturbation of the RB pathway, which induces a progenitor phenotype. In vitro and in vivo inactivation of Rb tumor suppression (TS) induces cortical astrocytes to proliferate rapidly, express progenitor markers, repress differentiation markers, and form self-renewing neurospheres that are susceptible to multi-lineage differentiation. This phenotype is sufficient to cause grade II astrocytomas which stochastically progress to GBM. Together with previous findings, these results demonstrate that cell susceptibility to GBM depends on the initiating driver. Frontiers Media S.A. 2022-06-24 /pmc/articles/PMC9263358/ /pubmed/35814428 http://dx.doi.org/10.3389/fonc.2022.904479 Text en Copyright © 2022 Adhikari, Sullivan, Bargaje, Lu, O’Sullivan, Song and Van Dyke https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Adhikari, Amit S.
Sullivan, Teresa
Bargaje, Rhishikesh
Lu, Lucy
O’Sullivan, T Norene
Song, Yurong
Van Dyke, Terry
Abrogation of Rb Tumor Suppression Initiates GBM in Differentiated Astrocytes by Driving a Progenitor Cell Program
title Abrogation of Rb Tumor Suppression Initiates GBM in Differentiated Astrocytes by Driving a Progenitor Cell Program
title_full Abrogation of Rb Tumor Suppression Initiates GBM in Differentiated Astrocytes by Driving a Progenitor Cell Program
title_fullStr Abrogation of Rb Tumor Suppression Initiates GBM in Differentiated Astrocytes by Driving a Progenitor Cell Program
title_full_unstemmed Abrogation of Rb Tumor Suppression Initiates GBM in Differentiated Astrocytes by Driving a Progenitor Cell Program
title_short Abrogation of Rb Tumor Suppression Initiates GBM in Differentiated Astrocytes by Driving a Progenitor Cell Program
title_sort abrogation of rb tumor suppression initiates gbm in differentiated astrocytes by driving a progenitor cell program
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263358/
https://www.ncbi.nlm.nih.gov/pubmed/35814428
http://dx.doi.org/10.3389/fonc.2022.904479
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