@article{dfb5898b5b804122910afdc01444227e,
title = "Crosstalk between ERK and MRTF-A signaling regulates TGFβ1-induced epithelial-mesenchymal transition",
abstract = "Epithelial-mesenchymal transition (EMT) is a physiological process that is essential during embryogenesis and wound healing and also contributes to pathologies including fibrosis and cancer. EMT is characterized by marked gene expression changes, loss of cell–cell contacts, remodeling of the cytoskeleton, and acquisition of enhanced motility. In the late stages of EMT, cells can exhibit myofibroblast-like properties with enhanced expression of the mesenchymal protein marker α-smooth muscle actin and contractile activity. Transforming growth factor (TGF)-β1 is a well-known inducer of EMT and it activates a plethora of signaling cascades including extracellular signal-regulated kinase (ERK). Previous reports have demonstrated a role for ERK signaling in the early stages of EMT, but the molecular impacts of ERK signaling on the late stages of EMT are still unknown. Here, we found that inhibition of the phosphorylation of ERK enhances focal adhesions, stress fiber formation, cell contractility, and gene expression changes associated with TGFβ1-induced EMT in mammary epithelial cells. These effects are mediated in part by the phosphorylation state and subcellular localization of myocardin-related transcription factor-A. These findings indicate that the intricate crosstalk between signaling cascades plays an important role in regulating the progression of EMT and suggests new approaches to control EMT processes.",
author = "Nalluri, {Sandeep M.} and Sankhe, {Chinmay S.} and O'Connor, {Joseph W.} and Blanchard, {Paul L.} and Khouri, {Joelle N.} and Phan, {Steven H.} and Gage Virgi and Gomez, {Esther W.}",
note = "Funding Information: This study was supported by start-up funds from the Pennsylvania State University (Penn State) and by the National Science Foundation (CMMI-1751785 to Esther W. Gomez). The authors would like to thank Dr. Justin Brown (Penn State) for use of the LI-COR Odyssey Imaging System for imaging western blots, Dr. Thomas Wood (Penn State), and Dr. Andrew Zydney (Penn State) for use of plate readers for protein analysis, and Dr. Micah Dembo (Boston University) for licensing LIBTRC 2.4 software. They would also like to thank Deborah Grove at the Penn State Genomics Core Facility—University Park, PA, for technical assistance with performing the quantitative real-time polymerase chain reaction experiments. Funding Information: This study was supported by start‐up funds from the Pennsylvania State University (Penn State) and by the National Science Foundation (CMMI‐1751785 to Esther W. Gomez). The authors would like to thank Dr. Justin Brown (Penn State) for use of the LI‐COR Odyssey Imaging System for imaging western blots, Dr. Thomas Wood (Penn State), and Dr. Andrew Zydney (Penn State) for use of plate readers for protein analysis, and Dr. Micah Dembo (Boston University) for licensing LIBTRC 2.4 software. They would also like to thank Deborah Grove at the Penn State Genomics Core Facility—University Park, PA, for technical assistance with performing the quantitative real‐time polymerase chain reaction experiments. Publisher Copyright: {\textcopyright} 2022 Wiley Periodicals LLC.",
year = "2022",
month = may,
doi = "10.1002/jcp.30705",
language = "English (US)",
volume = "237",
pages = "2503--2515",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "5",
}
