Carbonic anhydrase IX reduces E-cadherin-mediated adhesion of MDCK cells via interaction with beta-catenin.
Carbonic anhydrase IX (CA IX) is a cancer-associated transmembrane isoform of zinc metalloenzymes that catalyse interconversion between carbon dioxide and bicarbonate. CA IX is strongly induced by tumor hypoxia and has been proposed to participate in acidification of tumor microenvironment and in cell adhesion. To elucidate the cell adhesion-related role of CA IX, we investigated its subcellular localization and relationship to E-cadherin, a key adhesion molecule whose loss or destabilization is linked to tumor invasion. For this purpose, we generated MDCK cells with constitutive expression of human CA IX protein. During the monolayer formation, CA IX was localized to cell-cell contacts and its distribution in lateral membranes overlapped with E-cadherin. Calcium switch-triggered disruption and reconstitution of cell contacts resulted in relocalization of both CA IX and E-cadherin to cytoplasm and back to plasma membrane. A similar phenomenon was observed in hypoxia-treated and reoxygenated cells. Moreover, CA IX-expressing MDCK cells exhibited reduced cell adhesion capacity and lower levels of Triton-insoluble E-cadherin. Finally, CA IX was found to coprecipitate with beta-catenin. We conclude that CA IX has a capacity to modulate E-cadherin-mediated cell adhesion via interaction with beta-catenin, which could be of potential significance in hypoxia-induced tumor progression.
Centre of Molecular Medicine, Institute of Virology, Slovak Academy of Sciences, Dúbravská cesta 9, 845 05 Bratislava, Slovak Republic.
Eliska
E
Svastová
Norbert
N
Zilka
Miriam
M
Zat'ovicová
Adriana
A
Gibadulinová
Fedor
F
Ciampor
Jaromír
J
Pastorek
Silvia
S
Pastoreková
D000818:Animals; D000951:Antigens, Neoplasm / Q000502:physiology*; D015820:Cadherins / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication; D015687:Cell Hypoxia; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D004285:Dogs; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000166:cytology* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000502:physiology*; D009369:Neoplasms / Q000378:metabolism; D011233:Precipitin Tests; D021381:Protein Transport; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D051176:beta Catenin
D000951:Antigens, Neoplasm; D015820:Cadherins; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins; D015534:Trans-Activators; D051176:beta Catenin; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D002118:Calcium