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 invasion-promoter and invasion-suppressor complexes. The E-cadherin/catenin invasion-suppressor 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 beta-catenin. Phosphorylation is also implicated in transmembrane receptor signal transduction through the E-cadherin/catenin complex. E-cadherin 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 like 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 tamoxifen were shown to upregulate the functions of the E-cadherin/catenin complex including inhibition of invasion.
Vermeulen
S
S
Laboratory of Experimental Cancerology, University Hospital, Gent, Belgium.
Van Marck
V
V
Van Hoorde
L
L
Van Roy
F
F
Bracke
M
M
Mareel
M
M
D000818:Animals; D015820:Cadherins / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000187:drug effects / Q000378:metabolism / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control*; D011485:Protein Binding; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects*; D051178:alpha Catenin; D051176:beta Catenin
C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin