Schmitz A A, Govek E E, Böttner B, Van Aelst L
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 11724, USA.
Exp Cell Res. 2000 Nov 25;261(1):1-12. doi: 10.1006/excr.2000.5049.
The acquisition of a motile and invasive phenotype is an important step in the development of tumors and ultimately metastasis. This step requires the abrogation of cell-cell contacts, the remodeling of the extracellular matrix and of cell-matrix interactions, and finally the movement of the cell mediated by the actin cytoskeleton. Evidence for participation of Rho GTPases in migration and invasion is addressed in this review with emphasis on epithelial cells and the contribution of Rho GTPases toward tumor invasion. The Rho GTPases, including Rac, Cdc42, and Rho, have been implicated in the establishment of cell-cell contacts and of cell-matrix interactions crucial to attaining a fully polarized epithelial state, and they are known for their regulation of the actin cytoskeleton and transcriptional activation. Under aberrant conditions, however, they have been implicated in motility, invasion, and some aspects of metastasis. It is well known that Rho GTPases are activated by different classes of transmembrane receptors and that they transmit these signals to their effector proteins. These downstream targets include not only adaptor proteins and kinases which affect the actin cytoskeleton, but also transcription factors leading to expression of genes necessary for the drastic morphological changes which accompany these processes.
获得运动性和侵袭性表型是肿瘤发展乃至转移过程中的重要一步。这一步骤需要消除细胞间接触、重塑细胞外基质和细胞-基质相互作用，最终由肌动蛋白细胞骨架介导细胞运动。本文综述了Rho GTP酶参与迁移和侵袭的证据，重点关注上皮细胞以及Rho GTP酶对肿瘤侵袭的作用。Rho GTP酶，包括Rac、Cdc42和Rho，参与建立对实现完全极化上皮状态至关重要的细胞间接触和细胞-基质相互作用，它们以调节肌动蛋白细胞骨架和转录激活而闻名。然而，在异常情况下，它们与运动性、侵袭以及转移的某些方面有关。众所周知，Rho GTP酶由不同类型的跨膜受体激活，并将这些信号传递给它们的效应蛋白。这些下游靶点不仅包括影响肌动蛋白细胞骨架的衔接蛋白和激酶，还包括导致伴随这些过程的剧烈形态变化所需基因表达的转录因子。
