Glycoprotein 90K Promotes E-Cadherin Degradation in a Cell Density-Dependent Manner via Dissociation of E-Cadherin-p120-Catenin Complex.
Glycoprotein 90K (also known as LGALS3BP or Mac-2BP) is a tumor-associated protein, and high 90K levels are associated with poor prognosis in some cancers. To clarify the role of 90K as an indicator for poor prognosis and metastasis in epithelial cancers, the present study investigated the effect of 90K on ... an adherens junctional protein, E-cadherin, which is frequently absent or downregulated in human epithelial cancers. Treatment of certain cancer cells with 90K significantly reduced E-cadherin levels in a cell-population-dependent manner, and these cells showed decreases in cell adhesion and increases in invasive cell motility. Mechanistically, 90K-induced E-cadherin downregulation occurred via ubiquitination-mediated proteasomal degradation. 90K interacted with the E-cadherin-p120-catenin complex and induced its dissociation, altering the phosphorylation status of p120-catenin, whereas it did not associate with β-catenin. In subconfluent cells, 90K decreased membrane-localized p120-catenin and the membrane fraction of the p120-catenin. Particularly, 90K-induced E-cadherin downregulation was diminished in p120-catenin knocked-down cells. Taken together, 90K upregulation promotes the dissociation of the E-cadherin-p120-catenin complex, leading to E-cadherin proteasomal degradation, and thereby destabilizing adherens junctions in less confluent tumor cells. Our results provide a potential mechanism to explain the poor prognosis of cancer patients with high serum 90K levels.
Mesh Terms:
Antigens, Neoplasm, Biomarkers, Tumor, Caco-2 Cells, Cadherins, Carrier Proteins, Catenins, Cell Adhesion, Cell Count, Cell Line, Tumor, Cell Membrane, Down-Regulation, Female, Gene Expression Regulation, Neoplastic, Glycoproteins, HEK293 Cells, Humans, MCF-7 Cells, Male, Neoplasm Invasiveness, Neoplasms, Phosphorylation, Prognosis, Proteolysis
Antigens, Neoplasm, Biomarkers, Tumor, Caco-2 Cells, Cadherins, Carrier Proteins, Catenins, Cell Adhesion, Cell Count, Cell Line, Tumor, Cell Membrane, Down-Regulation, Female, Gene Expression Regulation, Neoplastic, Glycoproteins, HEK293 Cells, Humans, MCF-7 Cells, Male, Neoplasm Invasiveness, Neoplasms, Phosphorylation, Prognosis, Proteolysis
Int J Mol Sci
Date: Dec. 02, 2017
PubMed ID: 29207493
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