Changes in Adhesion Plaque Protein Levels Regulate Cell Motility And Tumorigenicity

Abstract

Cell adhesion to neighboring cells and to the extracellular matrix (ECM) plays a major role in cell and tissue morphogenesis (Edelman, 1992; Takeichi, 1991; Hynes, 1992). These complex, adhesion-related cellular processes are mediated through transmembrane contact receptors of the cadherin and integrin families of receptors (Takeichi, 1991; Hynes, 1992). In the cytoplasmic domain, these receptors interact with cytoskeletal plaque proteins such as vinculin, talin and α-actinin which anchor the microfilament system to junctional areas in adherens type junctions (AJ) in adhesion plaques, and to α and β catenin and plakoglobin in cell-cell AJ (Burridge et al., 1988; Geiger and Ginsberg, 1991; Geiger et al., 1992). The cascade of molecular interactions which links the outside to the inside of the cell defines cell shape and motility, and also has a function in signal transduction which results in effects on cell growth, differentiation, and gene expression (Ben-Ze’ev, 1991; 1992; Schwartz, 1992; Haskill and Juliano, 1993). Signaling through adhesion plaques is suggested to occur through changes in tyrosine phosphorylation (Burridge et al., 1992; Volberg et al., 1992). Moreover, recent studies have demonstrated that the changes in tyrosine phosphorylation of a cytoplasmic adhesion plaque tyrosine kinase (p125^FAK) is common to adhesion related signaling and to growth factor, cytokine and neuropeptide induced signaling (Zachary and Rozengurt, 1992), and that tyrosine phosphorylation of p125^FAK is constitutively activated in oncogene-transformed cells (Guan and Shalloway, 1992). These results suggest a convergence, in adhesion plaques, of signals transduced by cytokines, oncogenes and adhesion.