Cadherin switching: essential for behavioral but not morphological changes during an epithelium-to-mesenchyme transition.
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.
Maeda
Masato
M
Department of Oral Biology (College of Dentistry), University of Nebraska Medical Center, Omaha, NE 68198-7696, USA.
Johnson
Keith R
KR
Wheelock
Margaret J
MJ
D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000096:biosynthesis / Q000378:metabolism*; D002448:Cell Adhesion; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D048429:Cell Size; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003902:Detergents / Q000494:pharmacology; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D004848:Epithelium / Q000473:pathology*; D006801:Humans; D047468:Immunoprecipitation; D008321:Mammary Glands, Animal / Q000378:metabolism; D042361:Mammary Glands, Human / Q000166:cytology / Q000378:metabolism; D008648:Mesoderm / Q000473:pathology*; D051379:Mice; D008856:Microscopy, Fluorescence; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation; D014945:Wound Healing
D015820:Cadherins; D003902:Detergents; D016271:Proto-Oncogene Proteins c-myc; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1