The goal of this study was to define Na,K-ATPase α and β subunit isoform expression and
isozyme composition in colorectal cancer cells and liver metastases. The α1, α3, and β1
isoforms were the most highly expressed in tumor cells and metastases; in the plasma
membrane of non-neoplastic cells and mainly in a cytoplasmic location in tumor cells.
α1β1 and α3β1 isozymes found in tumor and metastatic cells exhibit the highest and
lowest Na+ affinity respectively and the highest K+ affinity. Mesenchymal cell isozymes
possess an intermediate Na+ affinity and a low K+ affinity. In cancer, these ions are
likely to favor optimal conditions for the function of nuclear enzymes involved in mitosis,
especially a high intra-nuclear K+ concentration. A major and striking finding of this study
was that in liver, metastasized CRC cells express the α3β1 isozyme. Thus, the α3β1
isozyme could potentially serve as a novel exploratory biomarker of CRC metastatic cells
in liver.
