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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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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. |
format | Online Article Text |
id | pubmed-9263358 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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