Cadherin-dependent organization and disorganization of epithelial architecture.
Epithelial cell layers exhibit an ordered polarized architecture. However, such structures are disrupted during malignant transformation, which generally coincides with a loss of regulate cell growth. We are investigating how the cadherin cell adhesion system controls these processes. Cadherins form a molecular complex with alpha-catenin, and beta-catenin or plakoglobin at the cytoplasmic side in normal cells. Lung carcinoma PC9 cells express E-cadherin. Although they express other catenins, they lack alpha-catenin and cannot firmly aggregate, suggesting that their E-cadherin is inactive. Transfection of the PC9 cells with alpha-catenin cDNA leads to activation of the E-cadherin, inducing their compact aggregation. In these aggregates, an almost complete epithelial-specific architecture is organized, including the formation of microvilli and a junctional complex. We also studied the effect of hepatocyte growth factor/scatter factor (HGF/SF) on cell-cell contacts in keratinocyte cell lines, and found that this growth factor can disrupt desmosomal cell-cell contacts. HGF/SF, and also epidermal growth factor, enhance tyrosine phosphorylation of beta-catenin or plakoglobin in human carcinoma lines as they induce scattering of these cells. These findings suggest that the cadherin adhesion system is central in organizing epithelial structures and that tyrosine phosphorylation of catenins may modulate this organization process.
Takeichi
M
M
Department of Biophysics, Faculty of Science, Kyoto University, Japan.
Watabe
M
M
Shibamoto
S
S
Ito
F
F
D015820:Cadherins / Q000502:physiology*; D002448:Cell Adhesion; D016764:Cell Polarity; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051180:Desmoplakins; D003896:Desmosomes / Q000187:drug effects / Q000648:ultrastructure; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D046911:Macromolecular Substances; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D014162:Transfection; D051178:alpha Catenin; D051185:gamma Catenin
C495273:CTNNA1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D046911:Macromolecular Substances; D051178:alpha Catenin; D051185:gamma Catenin; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor