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Science 21 November 1997:
Vol. 278. no. 5342, pp. 1464 - 1466
DOI: 10.1126/science.278.5342.1464
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Reports

Inhibition of Invasion of Epithelial Cells by Tiam1-Rac Signaling

Peter L. Hordijk, * Jean Paul ten Klooster, Rob A. van der Kammen, Frits Michiels, Lauran C. J. M. Oomen, John G. Collard dagger

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.

Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands.
*   Present address: Central Laboratory of the Red Cross Blood Transfusion Services, Plesmanlaan 125, 1066 CX Amsterdam, Netherlands.

dagger    To whom correspondence should be addressed. E-mail: JCOLL@NKI.NL

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Mol. Biol. Cell 11, 3703-3721
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Ankyrin-Tiam1 Interaction Promotes Rac1 Signaling and Metastatic Breast Tumor Cell Invasion and Migration.
L. Y.W. Bourguignon, H. Zhu, L. Shao, and Y. W. Chen (2000)
J. Cell Biol. 150, 177-192
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Oncogenic Ras Downregulates Rac Activity, which Leads to Increased Rho Activity and Epithelial-Mesenchymal Transition.
G. C.M. Zondag, E. E. Evers, J. P. ten Klooster, L. Janssen, R. A. van der Kammen, and J. G. Collard (2000)
J. Cell Biol. 149, 775-782
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Activation of Cdc42, Rac, PAK, and Rho-Kinase in Response to Hepatocyte Growth Factor Differentially Regulates Epithelial Cell Colony Spreading and Dissociation.
I. Royal, N. Lamarche-Vane, L. Lamorte, K. Kaibuchi, and M. Park (2000)
Mol. Biol. Cell 11, 1709-1725
   Abstract »    Full Text »
Restoration of Tight Junction Structure and Barrier Function by Down-Regulation of the Mitogen-activated Protein Kinase Pathway in Ras-transformed Madin-Darby Canine Kidney Cells.
Y.-h. Chen, Q. Lu, E. E. Schneeberger, and D. A. Goodenough (2000)
Mol. Biol. Cell 11, 849-862
   Abstract »    Full Text »
Regulation of Cadherin Adhesive Activity.
B. M. Gumbiner (2000)
J. Cell Biol. 148, 399-404
   Abstract »    Full Text »    PDF »
RhoA Function in Lamellae Formation and Migration Is Regulated by the {alpha}6{beta}4 Integrin and cAMP Metabolism.
K. L. O'Connor, B.-K. Nguyen, and A. M. Mercurio (2000)
J. Cell Biol. 148, 253-258
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CD44 Interaction with Tiam1 Promotes Rac1 Signaling and Hyaluronic Acid-mediated Breast Tumor Cell Migration.
L. Y. W. Bourguignon, H. Zhu, L. Shao, and Y. W. Chen (2000)
J. Biol. Chem. 275, 1829-1838
   Abstract »    Full Text »    PDF »
Synaptic development is controlled in the periactive zones of Drosophila synapses.
M Sone, E Suzuki, M Hoshino, D Hou, H Kuromi, M Fukata, S Kuroda, K Kaibuchi, Y Nabeshima, and C Hama (2000)
Development 127, 4157-4168
   Abstract »    PDF »
Rac1 mutations produce aberrant epithelial differentiation in the developing and adult mouse small intestine.
T. Stappenbeck and J. Gordon (2000)
Development 127, 2629-2642
   Abstract »    PDF »
Potentiation of Cell Migration by Adhesion-dependent Cooperative Signals from the GTPase Rac and Raf Kinase.
J. Leng, R. L. Klemke, A. C. Reddy, and D. A. Cheresh (1999)
J. Biol. Chem. 274, 37855-37861
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Altered states: Involvement of phosphorylated CagA in the induction of host cellular growth changes by Helicobacter pylori.
E. D. Segal, J. Cha, J. Lo, S. Falkow, and L. S. Tompkins (1999)
PNAS 96, 14559-14564
   Abstract »    Full Text »    PDF »


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