E-cadherin germline missense mutations and cell phenotype: evidence for the independence of cell invasion on the motile capabilities of the cells

Hum Mol Genet. 2003 Nov 15;12(22):3007-16. doi: 10.1093/hmg/ddg316. Epub 2003 Sep 18.


In Hereditary Diffuse Gastric Cancer syndrome, E-cadherin germline mutations of the missense type harbour significant functional consequences. In this study, we have characterised the effect of T340A, A617T, A634V and V832M E-cadherin germline missense mutations on cell morphology, motility and proliferation. Wild-type E-cadherin and A617T expressing cells have an epithelial-like morphology, with polarised cells migrating unidirectionally. T340A and A634V expressing cells, fibroblast-like, have a high motile phenotype. We show that this phenotype is dependent on an increased level of active RhoA. V832M expressing cells grow in piled-up structure of round cells, as an effect of the disturbance of the binding between alpha-catenin and beta-catenin. The destabilisation of the adhesion complex is shown to hamper the motile capabilities of these cells. We did not observe any effect of the E-cadherin mutations on cell proliferation. We show the existence of a genotype-phenotype correlation between different E-cadherin mutations and cell behaviour. However, we demonstrate that the ability of cells expressing the different E-cadherin mutations to invade is independent on their motile capabilities, providing evidence that motility is neither necessary nor sufficient for cells to invade. Our data give new insights into the understanding of the mechanisms linking invasion and E-cadherin mutations in diffuse gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism
  • Antigens, CD / metabolism
  • Blotting, Western
  • CHO Cells
  • Cadherins / genetics*
  • Cadherins / immunology
  • Cell Division
  • Cell Movement
  • Cell Polarity
  • Codon, Nonsense*
  • Collagen Type I / metabolism
  • Cricetinae
  • Cricetulus
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Fluorescent Antibody Technique, Direct
  • Germ-Line Mutation*
  • Models, Biological
  • Phenotype
  • Precipitin Tests
  • Pseudopodia / metabolism
  • rac1 GTP-Binding Protein / metabolism
  • rhoA GTP-Binding Protein / metabolism


  • Antibodies, Monoclonal
  • Antigens, CD
  • Cadherins
  • Codon, Nonsense
  • Collagen Type I
  • rac1 GTP-Binding Protein
  • rhoA GTP-Binding Protein