Na,K-ATPase beta-subunit is required for epithelial polarization, suppression of invasion, and cell motility.
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 alpha- and beta-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 beta(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 beta(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 beta-subunit's function to induce epithelial polarization and suppress invasiveness and motility of carcinoma cells. Involvement of the beta(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.
Rajasekaran
S A
SA
Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA.
Palmer
L G
LG
Quan
K
K
Harper
J F
JF
Ball
W J
WJ
Bander
N H
NH
Peralta Soler
A
A
Rajasekaran
A K
AK
D000199:Actins / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line / Q000821:virology; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology*; D002999:Clone Cells; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts; D007668:Kidney / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008980:Moloney murine sarcoma virus; D021122:Protein Subunits; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D015820:Cadherins; D021122:Protein Subunits; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase