Cadherin/catenin complex: a target for antiinvasive therapy?
Invasion is a major challenge for cancer therapy. Invasion or noninvasion 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 attractive as a target for a putative antiinvasive therapy because of its multifactorial regulation at multiple levels and sometimes in a reversible way. Mutations in the E-cadherin gene combined with loss of the wild type allele causes irreversible downregulation in some human cancers. Posttranslational and reversible downregulation may occur by tyrosine phosphorylation of beta-catenin. Phosphorylation is implicated also in transmembrane receptor signal transduction through the E-cadherin/catenin complex. Homophilic interaction with E-cadherin on another cell through a dimeric adhesion zipper, involving the HAV sequence of the first extracellular 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.
Mareel
M
M
Department of Radiotherapy and Nuclear Medicine, University Hospital, Gent, Belgium.
Berx
G
G
Van Roy
F
F
Bracke
M
M
D000818:Animals; D015820:Cadherins / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000502:physiology*; D051180:Desmoplakins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D015534:Trans-Activators; D051176:beta Catenin