Downregulation of cell surface CA125/MUC16 induces epithelial-to-mesenchymal transition and restores EGFR signalling in NIH:OVCAR3 ovarian carcinoma cells.
Br J Cancer
; 104(6): 989-99, 2011 Mar 15.
Article
en En
| MEDLINE
| ID: mdl-21326240
ABSTRACT
BACKGROUND:
Epithelial ovarian cancer (EOC) cells are prone to metastasise throughout the peritoneal cavity. The epithelial-to-mesenchymal transition (EMT) is a necessary step towards metastatic tumour progression. CA125/MUC16 mucin is a high-molecular-weight glycoprotein overexpressed in the majority of serous carcinomas, suggesting a possible role in the pathogenesis of these cancers.METHODS:
The role of CA125/MUC16 in EMT was investigated using single-chain antibody-mediated knockdown of cell surface CA125/MUC16 in overexpressing EOC NIHOVCAR3 cells.RESULTS:
CA125/MUC16 knockdown was associated with morphological alterations along with decreased surface expression of epithelial markers (E-cadherin, cytokeratin-18) and increased expression of mesenchymal markers (N-cadherin, vimentin). Co-immunoprecipitation experiments revealed that CA125/MUC16 binds to E-cadherin and ß-catenin complexes. The in vitro studies showed disruption of cell-cell junctions, enhanced motility, migration and invasiveness in CA125/MUC16 knockdown cells. Enhanced epidermal growth factor receptor (EGFR) activation was observed in CA125/MUC16 knockdown cells along with increased Akt and ERK1/2 phosphorylation, which are downstream effectors of EGFR, and increased MMP-2 and MMP-9 expression and activities. Epidermal growth factor receptor inhibition strongly inhibited the motility of CA125/MUC16 knockdown cells.CONCLUSIONS:
Our findings suggest that CA125/MUC16 plays a role in EMT, presumably through its interaction with E-cadherin and ß-catenin complexes and by modulating EGFR and its downstream signalling pathway in NIHOVCAR3 cells.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
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Carcinoma
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Antígeno Ca-125
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Transición Epitelial-Mesenquimal
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Receptores ErbB
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Proteínas de la Membrana
Tipo de estudio:
Evaluation_studies
Límite:
Female
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Humans
Idioma:
En
Año:
2011
Tipo del documento:
Article