INHIBITION OF INVASION OF EPITHELIAL-CELLS BY TIAM1-RAC SIGNALING

Tiam1 encodes an exchange factor for the Rho-like guanosine triphospha tase Rac. Both Tiam1 and activated RacV12 promote invasiveness of T ly mphoma cells. In epithelial Madin-Darby canine kidney (MDCK) cells, Ti am1 localized to adherens junctions. Ectopic expression of Tiam1 or Ra cV12 inhibited hepatocyte growth factor-induced scattering by increasi ng E-cadherin-mediated cell-cell adhesion accompanied by actin polymer ization at cell-cell contacts. In Ras-transformed MDCK cells, expressi on of Tiam1 or RacV12 restored E-cadherin-mediated adhesion, resulting in phenotypic reversion and loss of invasiveness. These data suggest an invasion-suppressor role for Tiam1 and Rac in epithelial cells.