Abstract
We recently isolated the Tiam1 gene from retrovirally mutagenized T-lymphoma cells (Cell 77, 537–549, 1994). The encoded Tiam1 protein harbors a Dbl homology (DH) domain, which is also present in activators (GDS) of Rho-like GTPases. These GTPases have been implicated in the regulation of the actin cytoskeleton in response to distinct extracellular stimuli and control the morphology, adhesion and motility of cells. Tiam1 indeed encodes an activator (GDS) of the Rho-like Rac protein (Nature, 1995 in press). Both, constitutive active V12Rac1 and Tiam1 induce invasiveness in T-lymphoma cells, suggesting that the Tiam1-induced invasion is caused by activation of Rac. Tiam1 induces a similar morphologically transformed phenotype in NIH3T3 fibroblasts as V12Rac1, including the formation of membrane ruffles. The Tiam1- and V12Rac1-transformed fibroblasts also produce tumors in nude mice. These studies implicate the Tiam1-Rac pathway in the process of tumor formation, invasion and metastasis.
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