A causal role for E-cadherin in the transition from adenoma to carcinoma

Nature. 1998 Mar 12;392(6672):190-3. doi: 10.1038/32433.


Development of malignant tumours is in part characterized by the ability of a tumour cell to overcome cell-cell adhesion and to invade surrounding tissue. E-cadherin is the main adhesion molecule of epithelia, and it has been implicated in carcinogenesis because it is frequently lost in human epithelial cancers. Re-establishing the functional cadherin complex in tumour cell lines results in a reversion from an invasive to a benign epithelial phenotype. However, it remained unresolved whether the loss of E-cadherin-mediated cell adhesion was a cause or a consequence of tumour progression in vivo. Here we report that the loss of E-cadherin expression coincides with the transition from well differentiated adenoma to invasive carcinoma in a transgenic mouse model of pancreatic beta-cell carcinogenesis (Rip1Tag2). Intercrossing Rip1Tag2 mice with transgenic mice that maintain E-cadherin expression in beta-tumour cells results in arrest of tumour development at the adenoma stage, whereas expression of a dominant-negative form of E-cadherin induces early invasion and metastasis. The results demonstrate that loss of E-cadherin-mediated cell adhesion is one rate-limiting step in the progression from adenoma to carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma, Islet Cell / pathology*
  • Animals
  • Cadherins / biosynthesis
  • Cadherins / physiology*
  • Carcinoma, Islet Cell / etiology*
  • Carcinoma, Islet Cell / pathology
  • Carcinoma, Islet Cell / secondary
  • Disease Models, Animal
  • Disease Progression
  • Humans
  • Immunoenzyme Techniques
  • Islets of Langerhans*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neoplasm Invasiveness
  • Pancreatic Neoplasms / etiology*
  • Pancreatic Neoplasms / pathology


  • Cadherins