HGF induces epithelial-to-mesenchymal transition by modulating the mammalian Hippo/MST2 and ISG15 pathways
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|Title:||HGF induces epithelial-to-mesenchymal transition by modulating the mammalian Hippo/MST2 and ISG15 pathways||Authors:||Farrell, Jennifer
Garcia Munoz, Amaya
Mehta, J. P.
Simpson, Jeremy C.
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||Journal:||Journal of Proteome Research||Volume:||13||Issue:||6||Start page:||2874||End page:||2886||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||metadata.dc.date.available:||2016-04-04T09:38:06Z|
|Appears in Collections:||Conway Institute Research Collection|
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