Details

Autor(en) / Beteiligte

• Schreiber, Susanne C
• Giehl, Klaudia
• Kastilan, Caroline
• Hasel, Cornelia
• Mühlenhoff, Martina
• Adler, Guido
• Wedlich, Doris
• Menke, Andre

Titel

Polysialylated NCAM Represses E-Cadherin-Mediated Cell-Cell Adhesion in Pancreatic Tumor Cells

Ist Teil von

• Gastroenterology (New York, N.Y. 1943), 2008-05, Vol.134 (5), p.1555-1566

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2008

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Background & Aims: 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. Methods: 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. Results: 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. Conclusions: 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.