Na,K-ATPase beta-subunit is required for epithelial polarization, suppression of invasion, and cell motility

• Published in: Molecular biology of the cell 2001-02, Vol.12 (2), p.279-295
• Main Authors: Rajasekaran, S A, Palmer, L G, Quan, K, Harper, J F, Ball, Jr, W J, Bander, N H, Peralta Soler, A, Rajasekaran, A K
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Actins - ultrastructure; Animals; Cadherins - genetics; Cadherins - metabolism; Cell Adhesion - physiology; Cell Line - virology; Cell Movement - physiology; Cell Polarity - physiology; Clone Cells; Cytoskeleton - metabolism; Cytoskeleton - ultrastructure; Dogs; Epithelial Cells - cytology; Epithelial Cells - metabolism; Epithelial Cells - pathology; Fibroblasts; Kidney - cytology; Kidney - metabolism; Kidney - pathology; Moloney murine sarcoma virus; Protein Subunits; Sodium - metabolism; Sodium-Potassium-Exchanging ATPase - genetics; Sodium-Potassium-Exchanging ATPase - metabolism
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.12.2.279

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.