Translation reprogramming by eIF3 linked to glioblastoma resistance
| Autor: | Nicolas Skuli, Christine Toulas, Solène M. Evrard, Stefania Millevoi, Monique Courtade-Saïdi, Anne Cammas, Meera Augustus, Julie Sesen, Erik Dassi, Juliette Bertorello, Elizabeth Cohen-Jonathan Moyal, Catherine Seva, Emmanuelle Uro-Coste, Julia Gilhodes |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
AcademicSubjects/SCI01140 AcademicSubjects/SCI01060 Protein subunit Cell AcademicSubjects/SCI00030 Brain tumor Cancer Translation (biology) General Medicine Standard Article Biology medicine.disease AcademicSubjects/SCI01180 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer cell medicine Cancer research Protein biosynthesis AcademicSubjects/SCI00980 Reprogramming |
| Zdroj: | NAR Cancer |
| ISSN: | 2632-8674 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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