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. 2016 Apr;127(2):253-60.
doi: 10.1007/s11060-015-2043-3. Epub 2016 Jan 5.

Impairment of stress granule assembly via inhibition of the eIF2alpha phosphorylation sensitizes glioma cells to chemotherapeutic agents

Fabrício de Almeida Souza Vilas-Boas  1 , Aristóbolo Mendes da Silva  2 , Lirlândia Pires de Sousa  3 , Kátia Maciel Lima  3 , Juliana Priscila Vago  3 , Lucas Felipe Fernandes Bittencourt  1 , Arthur Estanislau Dantas  4 , Dawidson Assis Gomes  4 , Márcia Carvalho Vilela  5 , Mauro Martins Teixeira  4 , Lucíola Silva Barcelos  6   7
Affiliations

Impairment of stress granule assembly via inhibition of the eIF2alpha phosphorylation sensitizes glioma cells to chemotherapeutic agents

Fabrício de Almeida Souza Vilas-Boas et al. J Neurooncol. 2016 Apr.

Abstract

Malignant gliomas are a lethal type of brain tumors that poorly respond to chemotherapeutic drugs. Several therapy resistance mechanisms have been characterized. However, the response to stress through mRNA translational control has not been evaluated for this type of tumor. A potential target would involve the alpha subunit of eukaryotic translation initiation factor (eIF2α) that leads to assembly of stress granules (SG) which are cytoplasmic granules mainly composed by RNA binding proteins and untranslated mRNAs. We assessed whether glioma cells are capable of assembling SG after exposure to different classes of chemotherapeutic agents through evaluation of the effects of interfering in this process by impairing the eIF2α signaling. C6 and U87MG cells were exposed to bortezomib, cisplatin, or etoposide. Forced expression of a dominant negative mutant of eIF2α (eIF2α(DN)) was employed to block this pathway. We observed that exposure to drugs stimulated SG assembly. This was reduced in eIF2α(DN)-transfected cells and this strategy enhanced chemotherapeutically-induced cell death for all drugs. Our data suggest that SG assembly occurs in glioma cells in response to chemotherapeutic drugs in an eIF2α-dependent manner and this response is relevant for drug resistance. Interfering with eIF2α signaling pathway may be a potential strategy for new co-adjuvant therapies to treat gliomas.

Keywords: Chemotherapy; Glioma; Integrated stress response; Stress granules; eIF2α.

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References

    1. Biochem Biophys Res Commun. 2005 Dec 2;337(4):1065-71 - PubMed
    1. Invest New Drugs. 2013 Oct;31(5):1169-81 - PubMed
    1. J Cell Biol. 1999 Dec 27;147(7):1431-42 - PubMed
    1. Clin Cancer Res. 2008 May 15;14(10):2900-8 - PubMed
    1. J Cell Sci. 2002 Aug 15;115(Pt 16):3227-34 - PubMed

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