Signaling of de-adhesion in cellular regulation and motility

Adhesion is a process that can be divided into three separate stages: (1) c ell attachment, (2) cell spreading, and (3) the formation of focal adhesion s and stress fibers. With each stage the adhesive strength of the cell incr eases. De-adhesion can be defined as the process involving the transition o f the cell from a strongly adherent state, characterized by focal adhesions and stress fibers, to a state of intermediate adherence, represented by a cell that is spread, but that lacks stress fibers terminating at adhesion p laques. We propose that this modification of the structural link between th e actin cytoskeleton and the extracellular matrix results in a more malleab le cellular state conducive for dynamic processes such as cytokinesis, mito genesis, and motility. Anti-adhesive proteins, including thrombospondin, te nascin, and SPARC, rapidly signal de-adhesion, potentially mediating prolif eration and migration during development and wound healing. Intracellular s ignaling molecules involved in the regulation of de-adhesion are only begin ning to be identified. Interestingly, many of the same signaling proteins r ecognized to play important roles during the process of adhesion have also been found to act during de-adhesion. Characterization of the precise mecha nisms by which these signals modulate adhesive structures and the cytoskele ton will further our understanding of the regulation of adhesive strength a nd its function in cellular physiology. (C) 1998 Wiley-Liss, Inc.