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

Synergistic effects of inhibiting the MNK-eIF4E and PI3K/ AKT/mTOR pathways on cell migration in MDA-MB-231 cells
Synergistic effects of inhibiting the MNK-eIF4E and PI3K/ AKT/mTOR pathways on cell migration in MDA-MB-231 cells
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.
cell signaling, Migration, kinase, dual inhibitors
1949-2553
14148-14159
Lineham, Ella
d00af20b-f6d7-4b92-96c6-0a717d46723a
Tizzard, Graham J.
8474c0fa-40df-43a6-a662-7f3c4722dbf2
Spencer, John
a3cf55cd-a4c7-4af6-b16c-96c8fb8c4cf4
Coles, Simon J.
3116f58b-c30c-48cf-bdd5-397d1c1fecf8
Morley, Simon J.
6d1f2ef0-4c65-4823-8b75-fe666ac4126a
Lineham, Ella
d00af20b-f6d7-4b92-96c6-0a717d46723a
Tizzard, Graham J.
8474c0fa-40df-43a6-a662-7f3c4722dbf2
Spencer, John
a3cf55cd-a4c7-4af6-b16c-96c8fb8c4cf4
Coles, Simon J.
3116f58b-c30c-48cf-bdd5-397d1c1fecf8
Morley, Simon J.
6d1f2ef0-4c65-4823-8b75-fe666ac4126a

Lineham, Ella, Tizzard, Graham J., Spencer, John, Coles, Simon J. and Morley, Simon J. (2018) Synergistic effects of inhibiting the MNK-eIF4E and PI3K/ AKT/mTOR pathways on cell migration in MDA-MB-231 cells. Oncotarget, 9 (18), 14148-14159. (doi:10.18632/oncotarget.24354).

Record type: Article

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.

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Accepted/In Press date: 25 January 2018
e-pub ahead of print date: 30 January 2018
Keywords: cell signaling, Migration, kinase, dual inhibitors

Identifiers

Local EPrints ID: 417814
URI: https://eprints.soton.ac.uk/id/eprint/417814
ISSN: 1949-2553
PURE UUID: 9ec180c4-d87f-4bea-904e-0e017cf31456
ORCID for Graham J. Tizzard: ORCID iD orcid.org/0000-0002-1577-5779
ORCID for Simon J. Coles: ORCID iD orcid.org/0000-0001-8414-9272

Catalogue record

Date deposited: 14 Feb 2018 17:30
Last modified: 06 Jun 2018 12:54

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Contributors

Author: Ella Lineham
Author: John Spencer
Author: Simon J. Coles ORCID iD
Author: Simon J. Morley

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