Digoxin promotes anoikis of circulating cancer cells by targeting Na⁺/K⁺-ATPase α3-isoform.

ABSTRACT: Circulating cancer cells (CCCs) are closely related to the process of distant metastasis. In early step of the metastasis cascade, CCCs must evade the detachment-induced cell death (anoikis) for their survival. Here, we examined whether Na⁺/K⁺-ATPase α3-isoform (α3NaK) in CCCs contributes to avoidance of anoikis. In CCCs isolated from gastric cancer patients, α3NaK was predominantly localized in the plasma membrane (PM), but it moved to the cytoplasm when the CCCs were attached to culture dishes. The CCCs showed significant expression of integrin α5 but not fibronectin, one of components of the extracellular matrix (ECM). In human gastric cancer MKN45 cells, digoxin (20 and 50 nM), a cardiac glycoside, significantly inhibited the enzyme activity and translocation (fro

SUBMITTER: Numata Y 

PROVIDER: S-EPMC12066707 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature