Coordination between TGF-β cellular signaling and epigenetic regulation during epithelial to mesenchymal transition

Congcong Lu, Simone Sidoli, Katarzyna Kulej, Karen Ross, Cathy H. Wu, Benjamin A. Garcia

Research output: Contribution to journalArticle

4 Scopus citations

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).

Original languageEnglish (US)
Article number11
JournalEpigenetics and Chromatin
Volume12
Issue number1
DOIs
StatePublished - Feb 8 2019
Externally publishedYes

Keywords

  • Combinatorial inhibition targeting signaling pathway and epigenetic regulator
  • Comprehensive profiling of histone modifications
  • Epithelial to mesenchymal transition
  • Erk signaling
  • Histone H3 lysine 27 trimethylation
  • Time-resolved quantitative (phospho)proteomics

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'Coordination between TGF-β cellular signaling and epigenetic regulation during epithelial to mesenchymal transition'. Together they form a unique fingerprint.

  • Cite this