CADHERIN CATENIN COMPLEX - A TARGET FOR ANTIINVASIVE THERAPY/

Invasion is a major challenge for cancer therapy. Invasion or noninvas ion results from the cross talk between cancer cells and host cells, b uilding 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 multifactor ial regulation at multiple levels and sometimes in a reversible way. M utations in the E-cadherin gene combined with loss of the wild type al lele causes irreversible downregulation in some human cancers. Posttra nslational and reversible downregulation may occur by tyrosine phospho rylation of beta-catenin. Phosphorylation is implicated also in transm embrane receptor signal transduction through the E-cadherin/catenin co mplex. Hemophilic interaction with E-cadherin on another cell through a dimeric adhesion zipper, involving the HAV sequence of the first ext racellular 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. (C) 1996 Wiley-Liss, Inc.