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HGF induces epithelial-to-mesenchymal transition by modulating the mammalian Hippo/MST2 and ISG15 pathways
Date Issued
2014-06-06
Date Available
2016-04-04T09:38:06Z
Abstract
Epithelial to mesenchymal transition (EMT) is a fundamental cell differentiation/dedifferentiation process which is associated with dramatic morphological changes. Formerly polarized and immobile epithelial cells which form cell junctions and cobblestone-like cell sheets undergo a transition into highly motile, elongated, mesenchymal cells lacking cell-to-cell adhesions. To explore how the proteome is affected during EMT we profiled protein expression and tracked cell biological markers in Madin-Darby kidney epithelial cells undergoing hepatocyte growth factor (HGF) induced EMT. We were able to identify and quantify over 4000 proteins by mass spectrometry. Enrichment analysis of this revealed that expression of proteins associated with the ubiquitination machinery was induced, whereas expression of proteins regulating apoptotic pathways was suppressed. We show that both the mammalian Hippo/MST2 and the ISG15 pathways are regulated at the protein level by ubiquitin ligases. Inhibition of the Hippo pathway by overexpression of either ITCH or A-Raf promotes HGF-induced EMT. Conversely, ISG15 overexpression is sufficient to induce cell scattering and an elongated morphology without external stimuli. Thus, we demonstrate for the first time that the Hippo/MST2 and ISG15 pathways are regulated during growth-factor induced EMT.
Sponsorship
Science Foundation Ireland
Type of Material
Journal Article
Publisher
American Chemical Society
Journal
Journal of Proteome Research
Volume
13
Issue
6
Start Page
2874
End Page
2886
Copyright (Published Version)
2014 American Chemical Society
Language
English
Status of Item
Peer reviewed
This item is made available under a Creative Commons License
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HGF induces epithelial to mesenchymal transition by modulating the mammalian HippoMST2 and ISG15 pathways.pdf
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1.33 MB
Format
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