[Mechanisms of cell adhesion and migration].
In order to understand the molecular mechanisms underlying cancer metastasis, it is important to clarify the mechanisms of cell adhesion and cell migration. When epithelial cells start to migrate, cell-cell junctions are first disrupted. During migration, membrane protrusions, such as lamellipodia and filopodia, are observed externally at the cell front, and retraction at the cell rear. In addition, dynamic reorganization of the actin cytoskeleton, such as disassembly and reassembly of stress fibers at cell-cell and cell-matrix junctions and membrane protrusions, is observed internally. Our experiments have demonstrated that the Rho and Rab family small G proteins coordinately regulate cell adhesion and migration of cultured MDCK cells. The Rho family consists of the Rho, Rac, and Cdc 42 subfamilies. The Rho subfamily regulates stress fiber formation, and integrin-based cell matrix adhesion. Furthermore, the Rac and Cdc 42 subfamilies regulate lamellipodia and filopodia formation, respectively, as well as cadherin-based cell-cell adhesion. The detailed modes of action of these small G proteins remain to be clarified; however, it is known that these proteins regulate cell adhesion and migration through reorganization of the actin cytoskeleton. The Rab family has over thirty members. We have found that some Rab family members are involved in HGF- or phorbol ester-induced endocytosis and exocytosis (recycling) of adhesion molecules such as integrin and cadherin. Endocytosis and exocytosis of these adhesion molecules are accompanied by disassembly and reassembly of the actin cytoskeleton, respectively, in a well coordinated manner. Thus, we propose the cooperative roles of the Rho and Rab families in cell adhesion and migration.
Kamei
T
T
Dept. of Molecular Biology and Biochemistry, Osaka University Medical School.
Matozaki
T
T
Takai
Y
Y
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D009362:Neoplasm Metastasis / Q000503:physiopathology; D009369:Neoplasms / Q000473:pathology
D015815:Cell Adhesion Molecules; D019204:GTP-Binding Proteins