REGULATION OF THE INVASION SUPPRESSOR FUNCTION OF THE CADHERIN CATENIN COMPLEX/

Invasion is the cause of cancer malignancy. Invasion results from the cross-talk between cancer cells and host cells, building molecular inv asion-promoter and invasion-suppressor complexes. The E-cadherin/caten in invasion-suppressor complex is regulated multifactorially, at multi ple levels and sometimes in a reversible way. Mutations in the E-cadhe rin gene combined with loss of the wild type allele, causing irreversi ble downregulation, has been demonstrated only in a minority of human cancers. Posttranslational and reversible downregulation has been ascr ibed to tyrosine phosphorylation of beta-catenin. Phosphorylation is a lso implicated in transmembrane receptor signal transduction through t he E-cadherin/catenin complex. E-cadherin interacts with E-cadherin on another cell through a dimeric adhesion zipper, involving the histidi ne-alanine-valine (HAV) sequence of the first extracellular domains. T his is the major extracellular link of the E-cadherin/catenin complex, though not the only one. Intracellularly, the list of proteins that b ind to or signal through the complex or through one or more of its ele ments is steadily growing. Extrinsic factors may influence the complex . At least in vitro, insulin-like growth factor-I, retinoic acid, tang eretin and tamoxifen were shown to upregulate the functions of the E-c adherin/catenin complex including inhibition of invasion.