The role of the E-cadherin/catenin adhesion complex in the development and progression of cancer

Mol Cell Biol Res Commun. 1999 Aug;2(2):77-85. doi: 10.1006/mcbr.1999.0155.

Abstract

The E-cadherin/catenin protein complex regulates the functional integrity of epithelia by mediating specific intercellular adhesion, Defects in the transmembrane E-cadherin protein play an important role in several human cancer types. E-cadherin-inactivating mutations were mainly found in sporadic lobular breast carcinoma and in both familial and sporadic diffuse gastric carcinoma. Armadillo proteins such as beta-catenin and p120ctn are complexed to the cytoplasmic tail of E-cadherin, whereas the vinculin-related alphaE-catenin protein forms a link to the actin cytoskeleton. The latter shows inactivating deletions in various tumor cell lines. Apparently, both E-cadherin and alphaE-catenin serve as tumor suppressor and invasion suppressor molecules. On the other hand, protein-stabilizing oncogenic mutations of beta-catenin were found at high frequency in particular human tumor types. Mutated beta-catenin protein is imported into the nucleus, and its binding to LEF/TCF transcription factors modulates transcription of intriguing target genes. Also p120ctn was recently found to arrive in the nucleus and to interact with a transcription factor. Furthermore, a wide variety of mechanisms have been described to regulate in a reversible way E-cadherin/catenin-mediated cell adhesion and differentiation. These phenomena appear to be crucial in human cancer development and progression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cadherins / physiology*
  • Catenins
  • Cell Adhesion Molecules / metabolism
  • Cell Nucleus / metabolism
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Humans
  • Neoplasms / etiology*
  • Neoplasms / pathology
  • Phosphoproteins / metabolism
  • Protein Processing, Post-Translational
  • Signal Transduction
  • Trans-Activators*
  • beta Catenin

Substances

  • CTNNB1 protein, human
  • Cadherins
  • Catenins
  • Cell Adhesion Molecules
  • Cytoskeletal Proteins
  • Phosphoproteins
  • Trans-Activators
  • beta Catenin
  • delta catenin