1. ¹Department of Internal Medicine I, University of Ulm, D-89081 Ulm, Germany
2. ²Institute of Zoology II, University of Karlsruhe, D-76131 Karlsruhe, Germany

Correspondence: A Menke, E-mail: andre.menke@medizin.uni-ulm.de

Received 26 June 2003; Revised 2 March 2004; Accepted 9 March 2004; Published online 26 April 2004.

Abstract

E-cadherin functions as suppressor of invasion in epithelial cells and its loss is described in many invasive carcinomas. In some tumours, the disappearance of E-cadherin has been correlated with upregulation of other classical cadherins, such as N- or P-cadherin. To analyse the different cellular functions of cadherin molecules, we stably expressed E-cadherin or N-cadherin in the E- and N-cadherin-deficient pancreatic tumour cell line MIA PaCa-2. Only E-cadherin was able to induce a mesenchymal–epithelial transition and suppressed invasion of MIA PaCa-2 cells. Furthermore, only re-expression of E-cadherin resulted in an upregulation of - and -catenin mRNAs and protein concentrations. Ectopically expressed N-cadherin failed to assemble cadherin/catenin adhesion complexes and failed to inhibit invasion. Analysis of p120^ctn, which was associated with both cadherins, demonstrated that E-cadherin was linked to a shorter isoform of p120^ctn. In contrast, N-cadherin was associated with the long, 120 kDa p120^ctn isoforms. In addition, p120^ctn connected with N-cadherin was phosphorylated at tyrosine residues, whereas the isoform linked to E-cadherin was not phosphorylated. Thus, the differences between E- and N-cadherin in recruiting different phosphorylated isoforms of p120^ctn to the membrane might be responsible for the inability of N-cadherin to replace E-cadherin as suppressor of invasion in pancreatic carcinoma cells.