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Vol. 12, Issue 2, 279-295, February 2001
-Subunit Is Required for Epithelial Polarization,
Suppression of Invasion, and Cell Motility
*Department of Pathology and Laboratory Medicine, University of
California, Los Angeles, Los Angeles, California 90095; Departments of
The cell adhesion molecule E-cadherin has been implicated in
maintaining the polarized phenotype of epithelial cells and suppression of invasiveness and motility of carcinoma cells. Na,K-ATPase, consisting of an Physiology and Urology, Weill Medical
College of Cornell University, New York, New York 10021;
Department of Cell Biology, The Scripps Research
Institute, La Jolla, California 92037; §Department of
Pharmacology and Cell Biophysics, University of Cincinnati Medical
Center, Cincinnati, Ohio 45267; and ¶Lankenau Medical
Research Center, Wynnewood, Pennsylvania 19096
- and 
-subunit, maintains the sodium gradient across the plasma membrane. A functional relationship between E-cadherin and Na,K-ATPase has not previously been described. We
present evidence that the Na,K-ATPase plays a crucial role in
E-cadherin-mediated development of epithelial polarity, and suppression of invasiveness and motility of carcinoma cells. Moloney sarcoma virus-transformed Madin-Darby canine kidney cells (MSV-MDCK) have highly reduced levels of E-cadherin and 1-subunit
of Na,K-ATPase. Forced expression of E-cadherin in MSV-MDCK cells did
not reestablish epithelial polarity or inhibit the invasiveness and
motility of these cells. In contrast, expression of E-cadherin and
Na,K-ATPase 1-subunit induced epithelial polarization,
including the formation of tight junctions and desmosomes, abolished
invasiveness, and reduced cell motility in MSV-MDCK cells. Our results
suggest that E-cadherin-mediated cell-cell adhesion requires the
Na,K-ATPase -subunit's function to induce epithelial polarization
and suppress invasiveness and motility of carcinoma cells. Involvement
of the 1-subunit of Na,K-ATPase in the polarized
phenotype of epithelial cells reveals a novel link between the
structural organization and vectorial ion transport function of
epithelial cells.
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