Yamazaki Daisuke, Kurisu Shusaku, Takenawa Tadaomi
Department of Biochemistry, Institute of Medical Science, University of Tokyo, Minato-ku, Japan.
Cancer Sci. 2005 Jul;96(7):379-86. doi: 10.1111/j.1349-7006.2005.00062.x.
Cell migration is a critical step in tumor invasion and metastasis, and regulation of this process will lead to appropriate therapies for treating cancer. Cancer cells migrate in various ways, according to cell type and degree of differentiation. The different types of cell migration are regulated by different mechanisms. Reorganization of the actin cytoskeleton is the primary mechanism of cell motility and is essential for most types of cell migration. Actin reorganization is regulated by Rho family small GTPases such as Rho, Rac, and Cdc42. These small GTPases transmit extracellular chemotactic signals to downstream effectors. Of these downstream effectors, Wiskott-Aldrich syndrome protein (WASP) family proteins are key regulators of cell migration. Activated WASP family proteins induce the formation of protrusive membrane structures involved in cell migration and degradation of the extracellular matrix. Inhibition of Rho family small GTPase signaling suppresses the migration and invasion of cancer cells. Thus, control of cell migration via the actin cytoskeleton provides the possibility of regulating cancer cell invasion and metastasis.
细胞迁移是肿瘤侵袭和转移的关键步骤,对这一过程的调控将为癌症治疗带来合适的疗法。癌细胞根据细胞类型和分化程度以多种方式迁移。不同类型的细胞迁移由不同机制调控。肌动蛋白细胞骨架的重组是细胞运动的主要机制,对大多数类型的细胞迁移至关重要。肌动蛋白重组由Rho家族小GTP酶如Rho、Rac和Cdc42调控。这些小GTP酶将细胞外趋化信号传递给下游效应器。在这些下游效应器中,威斯科特-奥尔德里奇综合征蛋白(WASP)家族蛋白是细胞迁移的关键调节因子。活化的WASP家族蛋白诱导参与细胞迁移和细胞外基质降解的突出膜结构的形成。抑制Rho家族小GTP酶信号传导可抑制癌细胞的迁移和侵袭。因此,通过肌动蛋白细胞骨架控制细胞迁移为调节癌细胞侵袭和转移提供了可能性。