Extracellular regulation of cancer invasion: the E-cadherin-catenin and other pathways

Biochem Soc Symp. 1999;65:43-62.

Abstract

The E-cadherin-catenin complex is pivotal for the regulation of cancer invasion. It not only serves cell-cell adhesion but also transduces signals from the micro-environment to other molecular complexes possibly implicated in invasion. Both functions are disturbed when the extracellular part of E-cadherin is cleaved off. Moreover, upon release into the environment, the E-cadherin fragments may interfere with intact complexes, as indicated by experiments with His-Ala-Val (HAV)-containing peptides that are homologous to parts of the first extracellular domain of E-cadherin. Scatter factor/hepatocyte growth factor (SF/HGF), on binding to its c-met tyrosine kinase receptor, can induce invasion through tyrosine phosphorylation of beta-catenin. SF/HGF-induced invasion is also associated with phosphorylation of pp125FAK, and both invasion and phosphorylation are inhibited by platelet-activating factor (PAF). Activation of the membrane-bound non-receptor tyrosine kinase pp60src can also induce invasion. Signal transduction pathways starting from pp60src include E-cadherin-associated beta-catenin as well as the focal adhesion kinase pp125FAK. Whereas all invasion-inducing pathways implicate phosphoinositide 3-kinase, the PAF pathway seems to be E-cadherin-catenin-independent. We conclude that cancer cell invasion is regulated by paracrine and autocrine factors that are released upon cross-talk with the host cells.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cadherins / metabolism*
  • Cytoskeletal Proteins / metabolism*
  • Extracellular Matrix / metabolism*
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Neoplasm Invasiveness*
  • Proto-Oncogene Proteins pp60(c-src) / metabolism
  • Trans-Activators*
  • beta Catenin

Substances

  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • Trans-Activators
  • beta Catenin
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins pp60(c-src)