Submembranous junctional plaque proteins include potential tumor suppressor molecules

T HE multistep theory of tumorigenesis is now widely accepted. During the tumor development the genetic alterations are accumulated, oncogenes are activated, and tumor suppressor genes are inactivated. Recently, the interesting idea is emerging that some cell adhesion molecules, integral membrane proteins, may work as tumor suppressors (Hedrick et al., 1993). Most of these cell adhesion molecules are known to be intimately associated with cytoskeletal proteins underlying plasma membranes (peripheral membrane proteins) to form a specialized membrane domain called a junctional apparatus including tight junctions (TJ) ~, adherens junctions (AJ), and desmosomes (DS) (Fig. 1). These peripheral membrane proteins concentrated in a "plaque" are thought to play a role in signal transduction from adhesion receptors (Juliano and Haskill, 1993) and in the regulation of adhesion molecules (Takeichi, 1991). Recently, the application of gene engineering techniques to plaque proteins has generated a wealth of novel observations, leading to the speculation that some of these proteins are required to suppress the development of tumors, i.e., act as a kind of "tumor suppressors" Here we review these findings and discuss some functions of the plaque proteins in normal cells as well as in tumorigenesis.