Thus, by nature, cell migration is a process of global Butenafine hydrochloride reorganization of cytoskeleton. For example, actin polymerization drives the formation and extension of the protrusions such as lamellipodia at the leading edge, while the asymmetric distribution and enzymatic engagement of myosin and actin produce the force for cellular contractility and lead to the retraction of the trailing edge. Rho small GTPases are clearly pivotal in all of these cytoskeletal rearrangement processes. For example, Rac is primarily responsible for generating a protrusive force through the localized actin polymerization, while Rho is responsible for the Tulathromycin B contraction of the cell body and the retraction of the rear end. As downstream effectors of Rho GTPases, cofilin severs actin filament to generate barbed ends and thus facilitates the actin treadmilling while Arp2/3 complex nucleates new actin filaments from the sides of preexisting filaments. The severing activity of cofilin and branching activity of Arp2/3 function coordinately to promote the formation of a branched actin network or cortical actin meshwork at the leading edge and generate propulsive force for migrating cells. The activation of Rho kinase, an effector of RhoA, leads to increased myosin phosphorylation and actomyosin contractility and therefore is required for the retraction process during cell movement. The profound morphological changes induced by KAI1/CD82 apparently resulted from the aberrant organization and/or reorganization of cellular cytoskeleton networks. Actin is the cytoskeleton system that drives the cell movement-related subcellular events including protrusion, traction, and retraction. As predicted, actin cytoskeleton became globally aberrant upon KAI1/CD82 overexpression. The reduced or deficient cortical meshwork and stress fibers in KAI1/CD82 overexpressing cells suggested the aberrancy in actin polymerization. Such aberrancy can be further exacerbated by the reduced integrin signaling in KAI1/CD82-overexpressing cells. The development of cortical actin network generates protrusive force, morphologically revealed as the lamellipodia formation. Therefore, the formation of actin cortical meshwork and simultaneous extension of leading lamellipodia are the major subcellular morphological features of many migrating cells. In KAI1/CD82-overexpressing Du145 cells, the loss of these morphological characteristics was apparently caused by aberrant actin organization, particularly the polymerization of branched, cortical actin meshwork. In parallel, the retraction process is also essential for the movement of many types of cells. The defects in retraction upon KAI1/CD82 expression were displayed as either elongated trailing tails when Du145-KAI1/CD82 cells were treated with HGF or spread on LN1-coated plates, long cellular extensions in the cells with bipolar or dumbbell shape, or persistent vertices in cells with irregular polygonal shape. Mechanistically, the deficiency in retraction could result from an abnormality of actinmyosin retraction machinery. In the case of KAI1/CD82, the decreased ROCK activity caused functional incompetence of this machinery while the fewer stress fibers made the retraction process lose its structural base. Rho small GTPases are the master regulators of actin reorganization. Rac activation stimulates membrane ruffling through polymerization of cortical actin near the cell periphery, while Rho activation stimulates cell contractility through assembly of mainly radial-oriented actin stress fibers.