A moving new role for the sodium pump in epithelial cells and carcinomas

The Na,K-ATPase, or sodium pump, is a ubiquitous plasma membrane protein in higher eukaryotes, including humans, that carries out the coupled active transport of Na+ ions out of the cell and of K+ ions into the cell, using the energy of hydrolysis of adenosine triphosphate. In recent years, it has been suggested that that this protein may also be involved in various other functions, such as transducing information from the extracellular milieu to intracellular signaling pathways, much like a growth factor receptor. It has also been suggested that the sodium pump may be essential to the formation and function of junctional complexes in epithelial cells, and, most recently, it has been shown to play a role in epithelial cell motility. Maloney sarcoma virus-transformed Madin Darby canine kidney cells have depressed Na,K-ATPase beta subunit abundance and enhanced motility as compared with untransformed cells. Repletion of Na,K-ATPase beta subunits in the transformed cells results in suppression of motility. The most recent work, discussed here, demonstrates that the Na,K-ATPase alpha and beta subunits play distinct and separate roles, interacting with proteins in the phosphatidylinositol 3-kinase pathway and leading to the remodeling of the cytoskeleton and lamellipodia formation. The sodium pump subunits thus seem to play a role in regulating carcinoma cell motility and may be involved in cell motility suppression in many epithelial cells.