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First published online 15 February 2005
doi: 10.1242/jcs.01634
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Research Article |
1 Department of Oral Biology (College of Dentistry), University of Nebraska Medical Center, Omaha, NE 68198-7696, USA
2 Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198-7696, USA
3 Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198-7696, USA
4 Department of Pathology and Microbiology (College of Medicine), University of Nebraska Medical Center, Omaha, NE 68198-7696, USA
5 Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-7696, USA
6 Eppley Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198-7696, USA
* Author for correspondence (e-mail: mwheelock{at}unmc.edu)
Accepted 4 November 2004
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 ß1 (TGF-ß1)-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-ß1. Moreover, these changes were reversible upon removal of TGF-ß1. 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-ß1-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.
Key words: Cadherin, TGF-ß, Epithelium-to-mesenchyme transition, Motility
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