Article

Polysialylated NCAM represses E-cadherin-mediated cell-cell adhesion in pancreatic tumor cells.

Institute of Zoology 2, University Karlsruhe, Karlsruhe, Germany.
Gastroenterology (impact factor: 11.68). 06/2008; 134(5):1555-66. DOI:10.1053/j.gastro.2008.02.023 pp.1555-66
Source: PubMed

ABSTRACT Inhibition of cell-cell adhesion between epithelial cells represents an early step during tumor metastasis. Down-regulation or perturbation of E-cadherin-mediated adherens junctions is an essential requirement in this process.
The interaction between polysialylated neural cell adhesion molecule (PSA-NCAM) and the E-cadherin adhesion complex was studied by coimmunoprecipitation assays. The presence of PSA-NCAM was correlated with tumor invasion by using cell-cell aggregation and cell migration assays. The importance of polysialic acid (PSA) in the interaction of NCAM with E-cadherin and inhibition of cell-cell adhesion was confirmed by enzymatic removal of PSA from NCAM and down-regulation of PSA-transferases by siRNA.
Expression of oncogenic K-Ras(V12) in pancreatic carcinoma cells resulted in induction of PSA-NCAM expression and reduced E-cadherin-mediated cellular adhesion. The association of PSA-NCAM with the E-cadherin adhesion complex correlated with decreased cell-cell aggregation and elevated cell migration of pancreatic carcinoma cells. Enzymatic removal of PSA from NCAM or reduction of polysialyltransferase expression led to reduced association between NCAM and E-cadherin and subsequently increased E-cadherin-mediated cell-cell aggregation and reduced cell migration.
Our data suggest the induction of PSA-NCAM by oncogenic K-Ras as a novel molecular mechanism by which E-cadherin-mediated cellular adhesion is reduced and dissemination of tumor cells is facilitated.

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Keywords

cell migration assays
 
cell-cell adhesion
 
cell-cell aggregation
 
coimmunoprecipitation assays
 
E-cadherin adhesion complex
 
E-cadherin adhesion complex correlated
 
E-cadherin-mediated adherens junctions
 
E-cadherin-mediated cell-cell aggregation
 
E-cadherin-mediated cellular adhesion
 
Enzymatic removal
 
epithelial cells
 
essential requirement
 
novel molecular mechanism
 
oncogenic K-Ras
 
oncogenic K-Ras(V12)
 
pancreatic carcinoma cells
 
polysialyltransferase expression
 
PSA-NCAM
 
PSA-NCAM expression
 
tumor cells