Na,K-ATPase activity promotes macropinocytosis in colon cancer via Wnt signaling.
Biol Open
; 13(5)2024 May 15.
Article
em En
| MEDLINE
| ID: mdl-38713004
ABSTRACT
Recent research has shown that membrane trafficking plays an important role in canonical Wnt signaling through sequestration of the ß-catenin destruction complex inside multivesicular bodies (MVBs) and lysosomes. In this study, we introduce Ouabain, an inhibitor of the Na,K-ATPase pump that establishes electric potentials across membranes, as a potent inhibitor of Wnt signaling. We find that Na,K-ATPase levels are elevated in advanced colon carcinoma, that this enzyme is elevated in cancer cells with constitutively activated Wnt pathway and is activated by GSK3 inhibitors that increase macropinocytosis. Ouabain blocks macropinocytosis, which is an essential step in Wnt signaling, probably explaining the strong effects of Ouabain on this pathway. In Xenopus embryos, brief Ouabain treatment at the 32-cell stage, critical for the earliest Wnt signal in development-inhibited brains, could be reversed by treatment with Lithium chloride, a Wnt mimic. Inhibiting membrane trafficking may provide a way of targeting Wnt-driven cancers.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pinocitose
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Neoplasias do Colo
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ATPase Trocadora de Sódio-Potássio
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Via de Sinalização Wnt
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Biol Open
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos