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Regulation of the Invasion Suppressor Function of the Cadherin/Catenin Complex

1996; Elsevier BV; Volume: 192; Issue: 7 Linguagem: Inglês

10.1016/s0344-0338(96)80091-4

1618-0631

Stefan Vermeulen, Veerle Van Marck, Leen Van Hoorde, Frans van Roy, Marc Bracke, Marcus Mareel,

Kruppel-like factors research

Invasion is the cause of cancer malignancy. Invasion results from the cross-talk between cancer cells and host cells, building molecular invasion-promoter and invasion-sup pressor complexes. The E-cadherin/catenin invasion-su ppressor complex is regulated multifactorially, at multiple levels and sometimes in a reversible way. Mutations in the E-cadherin gene combined with loss of the wild type allele, causing irreversible downregulation, has been demonstrated only in a minority of human cancers. Posttranslational and reversible downregulation has been ascribed to tyrosine phosphorylation of ß-catenin. Phosphorylation is also implicated in transmembrane receptor signal transduction through the E-cadherin/catenin complex. Ecadherin interacts with E-cadherin on another cell through a dimeric adhesion zipper, involving the histidine-alanine-valine (HAV) sequence of the first extracellular domains. This is the major extracellular link of the E-cadherin/catenin complex, though not the only one. Intracellularly, the list of proteins that bind to or signal through the complex or through one or more of its elements is steadily growing. Extrinsic factors may influence the complex. At least in vitro, insulin-like growth factor-I, retinoic acid, tangeretin and tamoxi fen were shown to upregulate the functions of the E-cadherin/catenin complex including inhibition of invasion.