| Modification Notes |
A gene designated Tiam1 was originally identified as an invasion-inducing gene by proviral tagging in combination with in vitro selection for invasiveness. Transfection of truncated Tiam1 cDNAs into noninvasive cells made these cells invasive. The predicted Tiam1 protein exhibits both Dbl and Pleckstrin-homologous domains characteristic of GDP-GTP exchange proteins for Rho-like proteins that have been implicated in cytoskeletal organization. In fibroblasts, Tiam1 induces a phenotype similar to that of constitutively activated (V12) Rac1, including membrane ruffling, and this is inhibited by dominant negative (N17) Rac1. Moreover, T lymphoma cells expressing (V12) Rac1 become invasive, supporting the suggestion that the Tiam1-Rac signaling pathway may be involved in the invasion and metastasis of tumor cells. |