HGF induces epithelial-to-mesenchymal transition by modulating the mammalian Hippo/MST2 and ISG15 pathways

Title: HGF induces epithelial-to-mesenchymal transition by modulating the mammalian Hippo/MST2 and ISG15 pathways
Authors: Farrell, Jennifer
Kelly, Ciara
Rauch, Jens
Kida, Katarzyna
Garcia Munoz, Amaya
Monsefi, Naser
Turriziani, Benedetta
Doherty, Carolanne
Mehta, J. P.
Matallanas, David
Simpson, Jeremy C.
Kolch, Walter
Kriegsheim, Alexander von
Permanent link: http://hdl.handle.net/10197/7540
Date: 6-Jun-2014
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.
Funding Details: Science Foundation Ireland
Type of material: Journal Article
Publisher: American Chemical Society
Copyright (published version): 2014 American Chemical Society
Keywords: Epithelial mesenchymal transition;Hippo-pathway;ISG5;SILAC;Quantitative expression proteomics;YAP1
DOI: 10.1021/pr5000285
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
Biology & Environmental Science Research Collection
SBI Research Collection
Medicine Research Collection

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