Inhibition of invasion of epithelial cells by Tiam1-Rac signaling.
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.
Hordijk
P L
PL
Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands.
ten Klooster
J P
JP
van der Kammen
R A
RA
Michiels
F
F
Oomen
L C
LC
Collard
J G
JG
D000199:Actins / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D002461:Cell Line, Transformed; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D003593:Cytoplasm / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D007365:Intercellular Junctions / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010641:Phenotype; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D020744:rac GTP-Binding Proteins
D000199:Actins; D015820:Cadherins; D011506:Proteins; D017228:Hepatocyte Growth Factor; D019204:GTP-Binding Proteins; D020744:rac GTP-Binding Proteins