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Mnk mediates integrin α6β4-dependent eIF4E phosphorylation and translation of VEGF mRNA.

Authors
Type
Published Article
Journal
Molecular Cancer Research
1557-3125
Publisher
American Association for Cancer Research
Publication Date
Volume
8
Issue
12
Pages
1571–1578
Identifiers
DOI: 10.1158/1541-7786.MCR-10-0091
PMID: 21047768
Source
Medline
License
Unknown

Abstract

It was previously shown that integrin α6β4 contributes to translation of cancer-related mRNAs such as VEGF via initiation factor eIF4E. In this study, we found that integrin α6β4 regulates the activity of eIF4E through the Ser/Thr kinase Mnk. Although a role for Mnk in various aspects of cancer progression has been established, a link between integrin and Mnk activity has not. Here we show that Mnk1 is a downstream effector of integrin α6β4 and mediates the α6β4 signaling, important for translational control. Integrin α6β4 signals through MEK and p38 MAPK to increase phosphorylation of Mnk1 and eIF4E. Inhibition of Mnk1 activity by CGP57380 or downregulation by shRNA blocks α6β4-dependent translation of VEGF mRNA. Our studies suggest that Mnk1 could be a therapeutic target in cancers where the integrin α6β4 level is high.

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