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

Mol Biol Cell. 2001 Feb;12(2):279-95. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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*


  • Actins
  • Cadherins
  • Protein Subunits
  • Sodium
  • Sodium-Potassium-Exchanging ATPase