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

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posted on 2023-06-09, 11:51 authored by Ella Lineham, Graham J Tizzard, Simon J Coles, John SpencerJohn Spencer, Simon Morley
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.

Funding

The re-modelling of mRNPs and the regulation of localised mRNA translation during mammalian cell attachment and spreading; G1479; BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCIL; BB/L018209/1

History

Publication status

  • Published

File Version

  • Published version

Journal

Oncotarget

ISSN

1949-2553

Publisher

Impact Journals

Issue

18

Volume

9

Page range

14148-14159

Department affiliated with

  • Biochemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2018-01-31

First Open Access (FOA) Date

2018-01-31

First Compliant Deposit (FCD) Date

2018-01-31

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