E-cadherin mediates adhesion and suppresses cell motility via distinct mechanisms.
Expression of the calcium-dependent adhesion molecule E-cadherin suppresses the invasion of cells in vitro, but the mechanism of this effect is unknown. To investigate this mechanism, we analyzed the effects of expressing E-cadherin in mouse L-cells and rat astrocyte-like WC5 cells. Increased cellular adhesion mediated by E-cadherin reduced invasion in WC5 cells and in some L-cells, but not in others. In all cases, suppression of invasion was correlated with decreased cell movement as assessed in an in vitro wound-filling assay and a transwell motility assay. To define the relationship between adhesion mediated by E-cadherin and suppression of motility, we analyzed the effects of deleting different regions of the E-cadherin cytoplasmic domain. E-cadherin lacking the entire cytoplasmic domain did not mediate calcium-dependent adhesion and did not reduce cell motility when expressed in WC5 cells. E-cadherin lacking a portion of the catenin-binding domain did not associate with the cytoskeleton and did not promote adhesion, yet still suppressed the motility of WC5 cells. In addition, E-cadherin that retains an intact catenin-binding domain, but lacks a juxtamembrane portion of the cytoplasmic domain, mediated effective adhesion, but did not suppress motility. These results indicate E-cadherin mediates adhesion and suppresses cell motility via distinct of E-cadherin plays a key role in suppressing motility.
Chen
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Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati College of Medicine, Ohio 45267-0521, USA.
Paradies
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Fedor-Chaiken
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Brackenbury
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D000595:Amino Acid Sequence; D000818:Animals; D015820:Cadherins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion; D002449:Cell Aggregation; D002460:Cell Line; D002465:Cell Movement; D003094:Collagen; D004338:Drug Combinations; D007739:L Cells; D007797:Laminin; D051379:Mice; D008969:Molecular Sequence Data; D011509:Proteoglycans; D014162:Transfection
D015820:Cadherins; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen