Regulation of Na,K-ATPase in Epithelial–Mesenchymal Transition and Cancer

Na,K-ATPase is an ion pump that creates an electrochemical gradient across the plasma membrane. In addition, Na,K-ATPase functions as a receptor and a signaling scaffold and its β-subunit has cell adhesion function. Many of the signaling pathways modulated by Na,K-ATPase have been linked to cell growth, apoptosis, cell adhesion, and motility. Changes in Na,K-ATPase function and expression have been reported in various cancers, even early during tumor development. Epithelial–mesenchymal transition (EMT) in which epithelial cells undergo a shift from a well-differentiated polarized epithelial phenotype to a fibroblastic, mesenchymal phenotype is one of the earliest steps in tumor progression. EMT can be induced by growth factors that activate signaling pathways to trigger an intricate network of transcriptional regulators. Interestingly, some of the transcription factors induced during EMT are known regulators of Na,K-ATPase expression. Here we summarize some of the best characterized EMT-inducing pathways, the transcription factors modulated by these signaling pathways and discuss how they may affect Na,K-ATPase subunit expression.