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Translation reprogramming by eIF3 linked to glioblastoma resistance
Intrinsic resistance to current therapies, leading to dismal clinical outcomes, is a hallmark of glioblastoma multiforme (GBM), the most common and aggressive brain tumor. Understanding the underlying mechanisms of such malignancy is, therefore, an urgent medical need. Deregulation of the protein tr...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210094/ https://www.ncbi.nlm.nih.gov/pubmed/34316689 http://dx.doi.org/10.1093/narcan/zcaa020 |
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author | Bertorello, Juliette Sesen, Julie Gilhodes, Julia Evrard, Solène Courtade-Saïdi, Monique Augustus, Meera Uro-Coste, Emmanuelle Toulas, Christine Moyal, Elizabeth Cohen-Jonathan Seva, Catherine Dassi, Erik Cammas, Anne Skuli, Nicolas Millevoi, Stefania |
author_facet | Bertorello, Juliette Sesen, Julie Gilhodes, Julia Evrard, Solène Courtade-Saïdi, Monique Augustus, Meera Uro-Coste, Emmanuelle Toulas, Christine Moyal, Elizabeth Cohen-Jonathan Seva, Catherine Dassi, Erik Cammas, Anne Skuli, Nicolas Millevoi, Stefania |
author_sort | Bertorello, Juliette |
collection | PubMed |
description | Intrinsic resistance to current therapies, leading to dismal clinical outcomes, is a hallmark of glioblastoma multiforme (GBM), the most common and aggressive brain tumor. Understanding the underlying mechanisms of such malignancy is, therefore, an urgent medical need. Deregulation of the protein translation machinery has been shown to contribute to cancer initiation and progression, in part by driving selective translational control of specific mRNA transcripts involved in distinct cancer cell behaviors. Here, we focus on eIF3, a multimeric complex with a known role in the initiation of translation and that is frequently deregulated in cancer. Our results show that the deregulated expression of eIF3e, the e subunit of eIF3, in specific GBM regions could impinge on selective protein synthesis impacting the GBM outcome. In particular, eIF3e restricts the expression of proteins involved in the response to cellular stress and increases the expression of key functional regulators of cell stemness. Such a translation program can therefore serve as a double-edged sword promoting GBM tumor growth and resistance to radiation. |
format | Online Article Text |
id | pubmed-8210094 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-82100942021-07-26 Translation reprogramming by eIF3 linked to glioblastoma resistance Bertorello, Juliette Sesen, Julie Gilhodes, Julia Evrard, Solène Courtade-Saïdi, Monique Augustus, Meera Uro-Coste, Emmanuelle Toulas, Christine Moyal, Elizabeth Cohen-Jonathan Seva, Catherine Dassi, Erik Cammas, Anne Skuli, Nicolas Millevoi, Stefania NAR Cancer Cancer Gene Regulation, Chromatin, and Epigenetics Intrinsic resistance to current therapies, leading to dismal clinical outcomes, is a hallmark of glioblastoma multiforme (GBM), the most common and aggressive brain tumor. Understanding the underlying mechanisms of such malignancy is, therefore, an urgent medical need. Deregulation of the protein translation machinery has been shown to contribute to cancer initiation and progression, in part by driving selective translational control of specific mRNA transcripts involved in distinct cancer cell behaviors. Here, we focus on eIF3, a multimeric complex with a known role in the initiation of translation and that is frequently deregulated in cancer. Our results show that the deregulated expression of eIF3e, the e subunit of eIF3, in specific GBM regions could impinge on selective protein synthesis impacting the GBM outcome. In particular, eIF3e restricts the expression of proteins involved in the response to cellular stress and increases the expression of key functional regulators of cell stemness. Such a translation program can therefore serve as a double-edged sword promoting GBM tumor growth and resistance to radiation. Oxford University Press 2020-09-17 /pmc/articles/PMC8210094/ /pubmed/34316689 http://dx.doi.org/10.1093/narcan/zcaa020 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of NAR Cancer. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Cancer Gene Regulation, Chromatin, and Epigenetics Bertorello, Juliette Sesen, Julie Gilhodes, Julia Evrard, Solène Courtade-Saïdi, Monique Augustus, Meera Uro-Coste, Emmanuelle Toulas, Christine Moyal, Elizabeth Cohen-Jonathan Seva, Catherine Dassi, Erik Cammas, Anne Skuli, Nicolas Millevoi, Stefania Translation reprogramming by eIF3 linked to glioblastoma resistance |
title | Translation reprogramming by eIF3 linked to glioblastoma resistance |
title_full | Translation reprogramming by eIF3 linked to glioblastoma resistance |
title_fullStr | Translation reprogramming by eIF3 linked to glioblastoma resistance |
title_full_unstemmed | Translation reprogramming by eIF3 linked to glioblastoma resistance |
title_short | Translation reprogramming by eIF3 linked to glioblastoma resistance |
title_sort | translation reprogramming by eif3 linked to glioblastoma resistance |
topic | Cancer Gene Regulation, Chromatin, and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210094/ https://www.ncbi.nlm.nih.gov/pubmed/34316689 http://dx.doi.org/10.1093/narcan/zcaa020 |
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