LIM-domain proteins in transforming growth factor β-induced epithelial-to-mesenchymal transition and myofibroblast differentiation

Cell Signal. 2012 Apr;24(4):819-25. doi: 10.1016/j.cellsig.2011.12.004. Epub 2011 Dec 11.

Abstract

Epithelial to mesenchymal transition (EMT) is a process during which junctions of the cell-cell contacts are dissolved, actin cytoskeleton is deformed, apical-basolateral cell polarity is lost and cell motility is increased. EMT is needed during normal embryonal development and wound healing, but may also lead to pathogenic transformation and formation of myofibroblasts. Transforming growth factor β (TGFβ) is a multifunctional cytokine promoting EMT and myofibroblast differentiation, and its dysregulation is involved in pathological disorders like cancer and fibrosis. Lin11, Isl-1 and Mec-3 (LIM) domain proteins are associated with actin cytoskeleton and linked to regulation of cell growth, damage signaling, cell fate determination and signal transduction. LIM-domain proteins generally do not bind DNA, but are more likely to function via protein-protein interactions. Despite being a disparate group of proteins, similarities in their functions are observed. In this review we will discuss the role of LIM-domain proteins in TGFβ-signaling pathway and in EMT-driven processes. LIM-domain proteins regulate TGFβ-induced actin cytoskeleton reorganization, motility and adhesion, but also dissolution of cell-cell junctions during EMT. Finally, the role of LIM-domain proteins in myofibroblasts found in fibrotic foci and tumor stroma will be discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Dedifferentiation
  • Cell Differentiation
  • Cell Movement
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Epithelial-Mesenchymal Transition / genetics*
  • Gene Expression Regulation*
  • Humans
  • Idiopathic Pulmonary Fibrosis / genetics
  • Idiopathic Pulmonary Fibrosis / metabolism*
  • Intercellular Junctions / genetics
  • Intercellular Junctions / metabolism
  • LIM Domain Proteins / genetics
  • LIM Domain Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Myofibroblasts / cytology
  • Myofibroblasts / metabolism
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Phosphorylation
  • Protein Binding
  • Signal Transduction / genetics
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Wound Healing / physiology*

Substances

  • LIM Domain Proteins
  • Transforming Growth Factor beta