Coordination between TGF-β cellular signaling and epigenetic regulation during epithelial to mesenchymal transition
Abstract Background Epithelial to mesenchymal transition (EMT) plays a crucial role in cancer propagation. It can be orchestrated by the activation of multiple signaling pathways, which have been found to be highly coordinated with many epigenetic regulators. Although the mechanism of EMT has been s...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2019-02-01
|
Series: | Epigenetics & Chromatin |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s13072-019-0256-y |
id |
doaj-400c5444f0884088b5a42b4e81dd8023 |
---|---|
record_format |
Article |
spelling |
doaj-400c5444f0884088b5a42b4e81dd80232020-11-25T01:13:07ZengBMCEpigenetics & Chromatin1756-89352019-02-0112111710.1186/s13072-019-0256-yCoordination between TGF-β cellular signaling and epigenetic regulation during epithelial to mesenchymal transitionCongcong Lu0Simone Sidoli1Katarzyna Kulej2Karen Ross3Cathy H. Wu4Benjamin A. Garcia5Epigenetics Institute, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of PennsylvaniaEpigenetics Institute, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of PennsylvaniaEpigenetics Institute, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of PennsylvaniaCenter for Bioinformatics and Computational Biology, Department of Computer and Information Sciences, University of DelawareCenter for Bioinformatics and Computational Biology, Department of Computer and Information Sciences, University of DelawareEpigenetics Institute, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of PennsylvaniaAbstract Background Epithelial to mesenchymal transition (EMT) plays a crucial role in cancer propagation. It can be orchestrated by the activation of multiple signaling pathways, which have been found to be highly coordinated with many epigenetic regulators. Although the mechanism of EMT has been studied over decades, cross talk between signaling and epigenetic regulation is not fully understood. Results Here, we present a time-resolved multi-omics strategy, which featured the identification of the correlation between protein changes (proteome), signaling pathways (phosphoproteome) and chromatin modulation (histone modifications) dynamics during TGF-β-induced EMT. Our data revealed that Erk signaling was activated in 5-min stimulation and structural proteins involved in cytoskeleton rearrangement were regulated after 1-day treatment, constituting a detailed map of systematic changes. The comprehensive profiling of histone post-translational modifications identified H3K27me3 as the most significantly up-regulated mark. We thus speculated and confirmed that a combined inhibition of Erk signaling and Ezh2 (H3K27me3 methyltransferase) was more effective in blocking EMT progress than individual inhibitions. Conclusions In summary, our data provided a more detailed map of cross talk between signaling pathway and chromatin regulation comparing to previous EMT studies. Our findings point to a promising therapeutic strategy for EMT-related diseases by combining Erk inhibitor (singling pathway) and Ezh2 inhibitor (epigenetic regulation).http://link.springer.com/article/10.1186/s13072-019-0256-yEpithelial to mesenchymal transitionTime-resolved quantitative (phospho)proteomicsComprehensive profiling of histone modificationsErk signalingHistone H3 lysine 27 trimethylationCombinatorial inhibition targeting signaling pathway and epigenetic regulator |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Congcong Lu Simone Sidoli Katarzyna Kulej Karen Ross Cathy H. Wu Benjamin A. Garcia |
spellingShingle |
Congcong Lu Simone Sidoli Katarzyna Kulej Karen Ross Cathy H. Wu Benjamin A. Garcia Coordination between TGF-β cellular signaling and epigenetic regulation during epithelial to mesenchymal transition Epigenetics & Chromatin Epithelial to mesenchymal transition Time-resolved quantitative (phospho)proteomics Comprehensive profiling of histone modifications Erk signaling Histone H3 lysine 27 trimethylation Combinatorial inhibition targeting signaling pathway and epigenetic regulator |
author_facet |
Congcong Lu Simone Sidoli Katarzyna Kulej Karen Ross Cathy H. Wu Benjamin A. Garcia |
author_sort |
Congcong Lu |
title |
Coordination between TGF-β cellular signaling and epigenetic regulation during epithelial to mesenchymal transition |
title_short |
Coordination between TGF-β cellular signaling and epigenetic regulation during epithelial to mesenchymal transition |
title_full |
Coordination between TGF-β cellular signaling and epigenetic regulation during epithelial to mesenchymal transition |
title_fullStr |
Coordination between TGF-β cellular signaling and epigenetic regulation during epithelial to mesenchymal transition |
title_full_unstemmed |
Coordination between TGF-β cellular signaling and epigenetic regulation during epithelial to mesenchymal transition |
title_sort |
coordination between tgf-β cellular signaling and epigenetic regulation during epithelial to mesenchymal transition |
publisher |
BMC |
series |
Epigenetics & Chromatin |
issn |
1756-8935 |
publishDate |
2019-02-01 |
description |
Abstract Background Epithelial to mesenchymal transition (EMT) plays a crucial role in cancer propagation. It can be orchestrated by the activation of multiple signaling pathways, which have been found to be highly coordinated with many epigenetic regulators. Although the mechanism of EMT has been studied over decades, cross talk between signaling and epigenetic regulation is not fully understood. Results Here, we present a time-resolved multi-omics strategy, which featured the identification of the correlation between protein changes (proteome), signaling pathways (phosphoproteome) and chromatin modulation (histone modifications) dynamics during TGF-β-induced EMT. Our data revealed that Erk signaling was activated in 5-min stimulation and structural proteins involved in cytoskeleton rearrangement were regulated after 1-day treatment, constituting a detailed map of systematic changes. The comprehensive profiling of histone post-translational modifications identified H3K27me3 as the most significantly up-regulated mark. We thus speculated and confirmed that a combined inhibition of Erk signaling and Ezh2 (H3K27me3 methyltransferase) was more effective in blocking EMT progress than individual inhibitions. Conclusions In summary, our data provided a more detailed map of cross talk between signaling pathway and chromatin regulation comparing to previous EMT studies. Our findings point to a promising therapeutic strategy for EMT-related diseases by combining Erk inhibitor (singling pathway) and Ezh2 inhibitor (epigenetic regulation). |
topic |
Epithelial to mesenchymal transition Time-resolved quantitative (phospho)proteomics Comprehensive profiling of histone modifications Erk signaling Histone H3 lysine 27 trimethylation Combinatorial inhibition targeting signaling pathway and epigenetic regulator |
url |
http://link.springer.com/article/10.1186/s13072-019-0256-y |
work_keys_str_mv |
AT congconglu coordinationbetweentgfbcellularsignalingandepigeneticregulationduringepithelialtomesenchymaltransition AT simonesidoli coordinationbetweentgfbcellularsignalingandepigeneticregulationduringepithelialtomesenchymaltransition AT katarzynakulej coordinationbetweentgfbcellularsignalingandepigeneticregulationduringepithelialtomesenchymaltransition AT karenross coordinationbetweentgfbcellularsignalingandepigeneticregulationduringepithelialtomesenchymaltransition AT cathyhwu coordinationbetweentgfbcellularsignalingandepigeneticregulationduringepithelialtomesenchymaltransition AT benjaminagarcia coordinationbetweentgfbcellularsignalingandepigeneticregulationduringepithelialtomesenchymaltransition |
_version_ |
1725163223933517824 |