Cadherin/catenin complex: a target for antiinvasive therapy?

J Cell Biochem. 1996 Jun 15;61(4):524-30. doi: 10.1002/(SICI)1097-4644(19960616)61:4%3C524::AID-JCB5%3E3.0.CO;2-Q.

Abstract

Invasion is a major challenge for cancer therapy. Invasion or noninvasion results from the cross talk between cancer cells and host cells, building molecular invasion-promoter and invasion-suppressor complexes. The E-cadherin/catenin invasion-suppressor complex is attractive as a target for a putative antiinvasive therapy because of its multifactorial regulation at multiple levels and sometimes in a reversible way. Mutations in the E-cadherin gene combined with loss of the wild type allele causes irreversible downregulation in some human cancers. Posttranslational and reversible downregulation may occur by tyrosine phosphorylation of beta-catenin. Phosphorylation is implicated also in transmembrane receptor signal transduction through the E-cadherin/catenin complex. Homophilic interaction with E-cadherin on another cell through a dimeric adhesion zipper, involving the HAV sequence of the first extracellular domains, is the major extracellular link of the E-cadherin/catenin complex. Intracellularly, the list of proteins that bind to or signal through the complex or one or more of its elements is growing. In vitro, insulin-like growth factor-I, and tamoxifen may upregulate the functions of the E-cadherin/catenin complex and inhibit invasion, demonstrating that this complex may serve as a target for antiinvasive therapy.

Publication types

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

MeSH terms

  • Animals
  • Cadherins / physiology*
  • Cytoskeletal Proteins / physiology*
  • Desmoplakins
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Neoplasm Invasiveness / prevention & control*
  • Signal Transduction / physiology
  • Trans-Activators*
  • beta Catenin

Substances

  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • Desmoplakins
  • Trans-Activators
  • beta Catenin