Cadherin-mediated cell-cell interactions in normal and cancer cells

Tissue Barriers. 2017 Jul 3;5(3):e1356900. doi: 10.1080/21688370.2017.1356900. Epub 2017 Jul 20.

Abstract

Adherens junctions (AJs) are molecular complexes that mediate cell-cell adhesive interactions and play pivotal roles in maintenance of tissue organization in adult organisms and at various stages of development. AJs consist of cadherin adhesion receptors, providing homophilic ligation with cadherins on adjacent cells, and members of the catenin protein family: p120, β- and α-catenin. α-catenin's linkage with the actin cytoskeleton defines the linear or punctate organization of AJs in different cell types. Myosin II-dependent tension drives vinculin recruitment by α-catenin and stabilizes the linkage of the cadherin/catenin complex to F-actin. Neoplastic transformation leads to prominent changes in the organization, regulation and stability of AJs. Epithelial-mesenchymal transition (EMT) whereby epithelial cells lose stable cell-cell adhesion, and reorganize their cytoskeleton to acquire migratory activity, plays the central role in cancer cell invasion and metastasis. Recent data demonstrated that a partial EMT resulting in a hybrid epithelial/mesenchymal phenotype with retention of E-cadherin is essential for cancer cell dissemination. E-cadherin and E-cadherin-based AJs are required for collective invasion and migration, survival in circulation, and metastatic outgrowth.

Keywords: E-cadherin; EMT; actin; adherens junctions; cancer cell dissemination; cell-cell adhesion.

Publication types

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

MeSH terms

  • Adherens Junctions / metabolism*
  • Animals
  • Cadherins / metabolism*
  • Cell Adhesion
  • Epithelial-Mesenchymal Transition
  • Humans
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Signal Transduction*
  • rap GTP-Binding Proteins / metabolism
  • rho GTP-Binding Proteins / metabolism

Substances

  • Cadherins
  • rap GTP-Binding Proteins
  • rho GTP-Binding Proteins