Crosstalk between ERK and MRTF-A signaling regulates TGFβ1-induced epithelial-mesenchymal transition

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.



Work Title Crosstalk between ERK and MRTF-A signaling regulates TGFβ1-induced epithelial-mesenchymal transition
Open Access
  1. Sandeep M. Nalluri
  2. Chinmay S. Sankhe
  3. Joseph W. O'Connor
  4. Paul L. Blanchard
  5. Joelle N. Khouri
  6. Steven H. Phan
  7. Gage Virgi
  8. Esther W. Gomez
License In Copyright (Rights Reserved)
Work Type Article
  1. Journal of Cellular Physiology
Publication Date May 1, 2022
Publisher Identifier (DOI)
Deposited July 19, 2022




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Work History

Version 1

  • Created
  • Added Nalluri_et_al_J_Cell_Physiol_manuscript_accepted.pdf
  • Added Creator Sandeep M. Nalluri
  • Added Creator Chinmay S. Sankhe
  • Added Creator Joseph W. O'Connor
  • Added Creator Paul L. Blanchard
  • Added Creator Joelle N. Khouri
  • Added Creator Steven H. Phan
  • Added Creator Gage Virgi
  • Added Creator Esther W. Gomez
  • Published