E- and N-cadherin differ with respect to their associated p120ctn isoforms and their ability to suppress invasive growth in pancreatic cancer cells

Oncogene. 2004 Jul 15;23(32):5532-42. doi: 10.1038/sj.onc.1207718.


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 alpha- and beta-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / metabolism*
  • Catenins
  • Cell Adhesion / physiology
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cytoskeletal Proteins / metabolism
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Trans-Activators / metabolism
  • alpha Catenin
  • beta Catenin


  • CTNNA1 protein, human
  • CTNNB1 protein, human
  • CTNNB1 protein, mouse
  • Cadherins
  • Catenins
  • Cell Adhesion Molecules
  • Ctnna1 protein, mouse
  • Cytoskeletal Proteins
  • Phosphoproteins
  • Protein Isoforms
  • Trans-Activators
  • alpha Catenin
  • beta Catenin
  • delta catenin