Rho-like GTPases: their role in cell adhesion and invasion.

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.