Michiels F, Collard J G
Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Biochem Soc Symp. 1999;65:125-46.
Metastasis formation is the leading cause of death in cancer patients. Using an in vitro model system, we have identified Tiam1 (T-lymphoma invasion and metastasis 1) as a gene that can induce invasion by and metastasis of mouse T-lymphoma cells. Subsequent studies showed that Tiam1 is a guanine nucleotide exchange factor for the Rho-like GTPase Rac1, a member of the Ras superfamily of small GTP-binding proteins. Rho-like GTPases play a pivotal role in the orchestration of changes in the actin cytoskeleton in response to receptor stimulation, but have also been shown to be involved in transcriptional activation and cell cycle regulation. Moreover, they can induce oncogenic transformation in fibroblast cells. In this chapter, we first summarize what is known about the signalling pathways that are activated by Tiam1 and Rho-like GTPases, and discuss the putative effectors that may mediate the effects in different cell types. In the latter part, we will more tentatively discuss the role of Tiam1 and Rho-like GTPases in invasion by and metastasis of tumour cells.
转移灶的形成是癌症患者死亡的主要原因。利用体外模型系统，我们已确定Tiam1（T淋巴瘤侵袭与转移因子1）是一种可诱导小鼠T淋巴瘤细胞侵袭和转移的基因。后续研究表明，Tiam1是Rho样GTP酶Rac1的鸟嘌呤核苷酸交换因子，Rac1是小GTP结合蛋白Ras超家族的成员。Rho样GTP酶在响应受体刺激时对肌动蛋白细胞骨架变化的协调中起关键作用，但也已被证明参与转录激活和细胞周期调控。此外，它们可诱导成纤维细胞发生致癌转化。在本章中，我们首先总结关于由Tiam1和Rho样GTP酶激活的信号通路的已知信息，并讨论可能介导不同细胞类型中效应的假定效应器。在后面部分，我们将更试探性地讨论Tiam1和Rho样GTP酶在肿瘤细胞侵袭和转移中的作用。
