Inhibition of Invasion of Epithelial Cells by Tiam1-Rac Signaling

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Science  21 Nov 1997:
Vol. 278, Issue 5342, pp. 1464-1466
DOI: 10.1126/science.278.5342.1464

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Tiam1 encodes an exchange factor for the Rho-like guanosine triphosphatase Rac. Both Tiam1 and activated RacV12 promote invasiveness of T lymphoma cells. In epithelial Madin–Darby canine kidney (MDCK) cells, Tiam1 localized to adherens junctions. Ectopic expression of Tiam1 or RacV12 inhibited hepatocyte growth factor–induced scattering by increasing E-cadherin–mediated cell-cell adhesion accompanied by actin polymerization at cell-cell contacts. In Ras-transformed MDCK cells, expression 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.

  • * Present address: Central Laboratory of the Red Cross Blood Transfusion Services, Plesmanlaan 125, 1066 CX Amsterdam, Netherlands.

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