Cadherin switching: essential for behavioral but not morphological changes during an epithelium-to-mesenchyme transition

J Cell Sci. 2005 Mar 1;118(Pt 5):873-87. doi: 10.1242/jcs.01634. Epub 2005 Feb 15.

Abstract

Epithelium-to-mesenchyme transitions (EMTs) are characterized by morphological and behavioral changes in cells. During an EMT, E-cadherin is downregulated while N-cadherin is upregulated. The goal of this study was to understand the role cadherin switching plays in EMT using a classical model system: transforming growth factor beta1 (TGF-beta1)-mediated EMT in mammary epithelial cells. We showed that stress fibers and focal adhesions are increased, and cell-cell junctions are decreased in response to TGF-beta1. Moreover, these changes were reversible upon removal of TGF-beta1. Downregulation of E-cadherin and upregulation of N-cadherin were both transcriptional. Neither experimental knockdown nor experimental overexpression of N-cadherin interfered with the morphological changes. In addition, the morphological changes associated with EMT preceded the downregulation of E-cadherin. Interestingly, TGF-beta1-induced motility in N-cadherin-knockdown cells was significantly reduced. Together, these data suggest that cadherin switching is necessary for increased motility but is not required for the morphological changes that accompany EMT.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adherens Junctions / metabolism
  • Animals
  • Cadherins / biosynthesis
  • Cadherins / metabolism*
  • Cell Adhesion
  • Cell Differentiation*
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Size
  • Cells, Cultured
  • Cloning, Molecular
  • Detergents / pharmacology
  • Down-Regulation
  • Electrophoresis, Polyacrylamide Gel
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Epithelium / pathology*
  • Humans
  • Immunoprecipitation
  • Mammary Glands, Animal / metabolism
  • Mammary Glands, Human / cytology
  • Mammary Glands, Human / metabolism
  • Mesoderm / pathology*
  • Mice
  • Microscopy, Fluorescence
  • Proto-Oncogene Proteins c-myc / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Transcription, Genetic
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta1
  • Up-Regulation
  • Wound Healing

Substances

  • Cadherins
  • Detergents
  • Proto-Oncogene Proteins c-myc
  • TGFB1 protein, human
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1