Adhesion Mediated Signaling: The Role of Junctional Plaque Proteins in the Regulation of Tumorigenesis

Abstract

Cell adhesion to neighboring cells and to the extracellular matrix (ECM) plays important roles in cell motility, growth, differentiation and survival (Ben-Ze’ev, 1997; Geiger et al., 1995; Gumbiner, 1996). The molecular interactions at cell adhesion sites include transmembrane integrin-type receptors that link cells to the ECM, and cadherin receptors at cell-cell contact sites that are associated with submembranal plaque proteins that bridge between the cytoskeleton and the adhesion receptors (Geiger et al., 1995). Major junctional plaque proteins are vinculin, α-actinin and the catenins. In addition, recent studies have amply indicated the localization in the submembranal plaque of a large number of regulatory molecules involved in signal transduction (Fig. 1, and Geiger et al., 1995; Gumbiner, 1996). The submembranal plaque area is now viewed not only as a structural link that mediates cell adhesion, but also as an important component in the control of signal transduction regulating cell behavior. Tumor cells are often characterized by altered adhesion, disorganized cytoskeletal assembly and impaired adhesion-mediated signaling (Ben-Ze’ev, 1985, 1992, 1997). Many cancer cells are “anchorage independent” and less susceptible to cell density-dependent inhibition of growth. Our previous studies have demonstrated that both the organization and expression of junctional plaque proteins is modulated during growth activation, differentiation and transformation (Ben-Ze’ev, 1991).