Synergistic effects of inhibiting the MNK-eIF4E and PI3K/AKT/mTOR pathways on cell migration in MDA-MB-231 cells

Lineham, Ella, Tizzard, Graham J, Coles, Simon J, Spencer, John and Morley, Simon (2018) Synergistic effects of inhibiting the MNK-eIF4E and PI3K/AKT/mTOR pathways on cell migration in MDA-MB-231 cells. Oncotarget. ISSN 1949-2553

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Abstract

The study of eukaryotic initiation factor 4E (eIF4E) is a key focus in cancer research due to its role in controlling the translation of tumour-associated proteins, that drive an aggressive migratory phenotype. eIF4E is a limiting component of the eIF4F complex which is a critical determinant for the translation of mRNAs. Mitogenactivated protein kinase interacting protein kinases (MNK1/2) phosphorylate eIF4E on Ser209, promoting the expression of oncogenic proteins, whereas mTORC1 phosphorylates and de-activates the eIF4E inhibitor, 4E-BP1, to release translational repression. Here we show that inhibiting these pathways simultaneously effectively slows the rate of cell migration in breast cancer cells. However, a molecular hybridisation approach using novel, cleavable dual MNK1/2 and PI3K/mTOR inhibiting hybrid agents was less effective at slowing cell migration.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Subjects: R Medicine > RM Therapeutics. Pharmacology > RM0300 Drugs and their actions
Depositing User: John Spencer
Date Deposited: 31 Jan 2018 16:54
Last Modified: 31 Jan 2018 16:54
URI: http://sro.sussex.ac.uk/id/eprint/73260

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Project NameSussex Project NumberFunderFunder Ref
The re-modelling of mRNPs and the regulation of localised mRNA translation during mammalian cell attachment and spreadingG1479BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCILBB/L018209/1