Repression of Na,K-ATPase beta1-subunit by the transcription factor snail in carcinoma

Mol Biol Cell. 2004 Mar;15(3):1364-73. doi: 10.1091/mbc.e03-09-0646. Epub 2003 Dec 29.


The Na,K-ATPase consists of two essential alpha- and beta-subunits and regulates the intracellular Na+ and K+ homeostasis. Although the alpha-subunit contains the catalytic activity, it is not active without functional beta-subunit. Here, we report that poorly differentiated carcinoma cell lines derived from colon, breast, kidney, and pancreas show reduced expression of the Na,K-ATPase beta1-subunit. Decreased expression of beta1-subunit in poorly differentiated carcinoma cell lines correlated with increased expression of the transcription factor Snail known to down-regulate E-cadherin. Ectopic expression of Snail in well-differentiated epithelial cell lines reduced the protein levels of E-cadherin and beta1-subunit and induced a mesenchymal phenotype. Reduction of Snail expression in a poorly differentiated carcinoma cell line by RNA interference increased the levels of Na,K-ATPase beta1-subunit. Furthermore, Snail binds to a noncanonical E-box in the Na,K-ATPase beta1-subunit promoter and suppresses its promoter activity. These results suggest that down-regulation of Na,K-ATPase beta1-subunit and E-cadherin by Snail are associated with events leading to epithelial to mesenchymal transition.

Publication types

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

MeSH terms

  • Animals
  • Cadherins / metabolism
  • Carcinoma / enzymology*
  • Cell Differentiation / physiology
  • DNA-Binding Proteins / metabolism*
  • Dogs
  • Down-Regulation / genetics*
  • E-Box Elements / genetics
  • Electrophoretic Mobility Shift Assay
  • Epithelial Cells / enzymology*
  • Gene Expression Regulation, Enzymologic / physiology
  • Humans
  • Promoter Regions, Genetic / genetics
  • Protein Subunits / metabolism
  • Snail Family Transcription Factors
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured


  • Cadherins
  • DNA-Binding Proteins
  • Protein Subunits
  • Snail Family Transcription Factors
  • Transcription Factors
  • Sodium-Potassium-Exchanging ATPase