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

Masato Maeda, Keith R. Johnson, Margaret J. Wheelock

Research output: Contribution to journalArticlepeer-review

347 Scopus citations

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 β1 (TGF-β1)-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-β1. Moreover, these changes were reversible upon removal of TGF-β1. 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-β1-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.

Original languageEnglish (US)
Pages (from-to)873-887
Number of pages15
JournalJournal of cell science
Volume118
Issue number5
DOIs
StatePublished - Mar 1 2005

Keywords

  • Cadherin
  • Epithelim-to-mesenchyme transition
  • Motility
  • TGF-β

ASJC Scopus subject areas

  • Cell Biology

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