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 th e polarized phenotype of epithelial cells and suppression of invasiveness a nd motility of carcinoma cells. Na,K-ATPase, consisting of an alpha- and be ta -subunit, maintains the sodium gradient across the plasma membrane. A fu nctional relationship between E-cadherin and Na,K-ATPase has not previously been described. We present evidence that the Na,K-ATPase plays a crucial r ole in E-cadherin-mediated development of epithelial polarity, and suppress ion 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, express ion of E-cadherin and Na,K-ATPase beta (1)-subunit induced epithelial polar ization, including the formation of tight junctions and desmosomes, abolish ed invasiveness, and reduced cell motility in MSV-MDCK cells. Our results s uggest that E-cadherin-mediated cell-cell adhesion requires the Na,K-ATPase beta -subunit's function to induce epithelial polarization and suppress in vasiveness and motility of carcinoma cells. Involvement of the beta (1)-sub unit of Na,K-ATPase in the polarized phenotype of epithelial cells reveals a novel link between the structural organization and vectorial ion transpor t function of epithelial cells.