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Vol. 9, Issue 8, 2185-2200, August 1998
Ludwig Institute for Cancer Research, University College London
Branch, London W1P 8BT, United Kingdom; and Department of Biochemistry
and Molecular Biology, University College London, London WC1E 6BT,
United Kingdom
Hepatocyte growth factor/scatter factor (HGF/SF) stimulates the
motility of epithelial cells, initially inducing centrifugal spreading
of colonies followed by disruption of cell-cell junctions and
subsequent cell scattering. In Madin-Darby canine kidney cells, HGF/SF-induced motility involves actin reorganization mediated by Ras,
but whether Ras and downstream signals regulate the breakdown of
intercellular adhesions has not been established. Both HGF/SF and
V12Ras induced the loss of the adherens junction proteins E-cadherin
and 
-catenin from intercellular junctions during cell spreading, and
the HGF/SF response was blocked by dominant-negative N17Ras. Desmosomes
and tight junctions were regulated separately from adherens junctions,
because they were not disrupted by V12Ras. MAP kinase,
phosphatidylinositide 3-kinase (PI 3-kinase), and Rac were required
downstream of Ras, because loss of adherens junctions was blocked by
the inhibitors PD098059 and LY294002 or by dominant-inhibitory mutants
of MAP kinase kinase 1 or Rac1. All of these inhibitors also
prevented HGF/SF-induced cell scattering. Interestingly, activated Raf
or the activated p110
subunit of PI 3-kinase alone did not induce
disruption of adherens junctions. These results indicate that
activation of both MAP kinase and PI 3-kinase by Ras is required for
adherens junction disassembly and that this is essential for the motile
response to HGF/SF.
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 J. G. N. Garcia, K. L. Schaphorst, A. D. Verin, S. Vepa, C. E. Patterson, and V. Natarajan Diperoxovanadate alters endothelial cell focal contacts and barrier function: role of tyrosine phosphorylation J Appl Physiol, December 1, 2000; 89(6): 2333 - 2343. [Abstract] [Full Text] [PDF]
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C. R. Maroun, M. A. Naujokas, M. Holgado-Madruga, A. J. Wong, and M. Park The Tyrosine Phosphatase SHP-2 Is Required for Sustained Activation of Extracellular Signal-Regulated Kinase and Epithelial Morphogenesis Downstream from the Met Receptor Tyrosine Kinase Mol. Cell. Biol., November 15, 2000; 20(22): 8513 - 8525. [Abstract] [Full Text]
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V. M.M. Braga, M. Betson, X. Li, and N. Lamarche-Vane Activation of the Small GTPase Rac Is Sufficient to Disrupt Cadherin-dependent Cell-Cell Adhesion in Normal Human Keratinocytes Mol. Biol. Cell, November 1, 2000; 11(11): 3703 - 3721. [Abstract] [Full Text]
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R. Paumelle, D. Tulasne, C. Leroy, J. Coll, B. Vandenbunder, and V. Fafeur Sequential Activation of ERK and Repression of JNK by Scatter Factor/Hepatocyte Growth Factor in Madin-Darby Canine Kidney Epithelial Cells Mol. Biol. Cell, November 1, 2000; 11(11): 3751 - 3763. [Abstract] [Full Text]
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T. M. Fournier, L. Lamorte, C. R. Maroun, M. Lupher, H. Band, W. Langdon, and M. Park Cbl-transforming Variants Trigger a Cascade of Molecular Alterations That Lead to Epithelial Mesenchymal Conversion Mol. Biol. Cell, October 1, 2000; 11(10): 3397 - 3410. [Abstract] [Full Text]
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B. Boettner, E.-E. Govek, J. Cross, and L. Van Aelst The junctional multidomain protein AF-6 is a binding partner of the Rap1A GTPase and associates with the actin cytoskeletal regulator profilin PNAS, August 1, 2000; 97(16): 9064 - 9069. [Abstract] [Full Text] [PDF]
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 L. TRUSOLINO, S. CAVASSA, P. ANGELINI, M. Ò, A. BERTOTTI, P. M. COMOGLIO, and C. BOCCACCIO HGF/scatter factor selectively promotes cell invasion by increasing integrin avidity FASEB J, August 1, 2000; 14(11): 1629 - 1640. [Abstract] [Full Text]
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N. Sheibani, C. M. Sorenson, and W. A. Frazier Differential Modulation of Cadherin-mediated Cell-Cell Adhesion by Platelet Endothelial Cell Adhesion Molecule-1 Isoforms through Activation of Extracellular Regulated Kinases Mol. Biol. Cell, August 1, 2000; 11(8): 2793 - 2802. [Abstract] [Full Text]
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J. Suzuki, Y. Yamazaki, L. Guang, Y. Kaziro, and H. Koide Involvement of Ras and Ral in Chemotactic Migration of Skeletal Myoblasts Mol. Cell. Biol., July 1, 2000; 20(13): 4658 - 4665. [Abstract] [Full Text]
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W. Cai, S. L. Rook, Z. Y. Jiang, N. Takahara, and L. P. Aiello Mechanisms of Hepatocyte Growth Factor-Induced Retinal Endothelial Cell Migration and Growth Invest. Ophthalmol. Vis. Sci., June 1, 2000; 41(7): 1885 - 1893. [Abstract] [Full Text]
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I. Royal, N. Lamarche-Vane, L. Lamorte, K. Kaibuchi, and M. Park Activation of Cdc42, Rac, PAK, and Rho-Kinase in Response to Hepatocyte Growth Factor Differentially Regulates Epithelial Cell Colony Spreading and Dissociation Mol. Biol. Cell, May 1, 2000; 11(5): 1709 - 1725. [Abstract] [Full Text]
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J.-F. Lai, S.-C. Kao, S.-T. Jiang, M.-J. Tang, P.-C. Chan, and H.-C. Chen Involvement of Focal Adhesion Kinase in Hepatocyte Growth Factor-induced Scatter of Madin-Darby Canine Kidney Cells J. Biol. Chem., March 10, 2000; 275(11): 7474 - 7480. [Abstract] [Full Text] [PDF]
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 T. Brabletz, K. Herrmann, A. Jung, G. Faller, and T. Kirchner Expression of Nuclear {beta}-Catenin and c-myc Is Correlated with Tumor Size but Not with Proliferative Activity of Colorectal Adenomas Am. J. Pathol., March 1, 2000; 156(3): 865 - 870. [Abstract] [Full Text] [PDF]
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Y.-h. Chen, Q. Lu, E. E. Schneeberger, and D. A. Goodenough 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 Mol. Biol. Cell, March 1, 2000; 11(3): 849 - 862. [Abstract] [Full Text]
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M Cozzolino, B Giovannone, A Serafino, K Knudsen, A Levi, S Alema, and A Salvatore Activation of TrkA tyrosine kinase in embryonal carcinoma cells promotes cell compaction, independently of tyrosine phosphorylation of catenins J. Cell Sci., January 5, 2000; 113(9): 1601 - 1610. [Abstract] [PDF]
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 M. P. Quinlan and J. L. Hyatt Establishment of the Circumferential Actin Filament Network Is a Prerequisite for Localization of the Cadherin-Catenin Complex in Epithelial Cells Cell Growth Differ., December 1, 1999; 10(12): 839 - 854. [Abstract] [Full Text]
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P. L. Woo, D. Ching, Y. Guan, and G. L. Firestone Requirement for Ras and Phosphatidylinositol 3-Kinase Signaling Uncouples the Glucocorticoid-induced Junctional Organization and Transepithelial Electrical Resistance in Mammary Tumor Cells J. Biol. Chem., November 12, 1999; 274(46): 32818 - 32828. [Abstract] [Full Text] [PDF]
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J. Espada, M. Perez-Moreno, V. M.M. Braga, P. Rodriguez-Viciana, and A. Cano H-Ras Activation Promotes Cytoplasmic Accumulation and Phosphoinositide 3-OH Kinase Association of {beta}-Catenin in Epidermal Keratinocytes J. Cell Biol., September 6, 1999; 146(5): 967 - 980. [Abstract] [Full Text] [PDF]
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R. Montesano, J. V. Soriano, G. Hosseini, M. S. Pepper, and H. Schramek Constitutively Active Mitogen-activated Protein Kinase Kinase MEK1 Disrupts Morphogenesis and Induces an Invasive Phenotype in Madin-Darby Canine Kidney Epithelial Cells Cell Growth Differ., May 1, 1999; 10(5): 317 - 332. [Abstract] [Full Text]
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M. Z. Hossain, A. B. Jagdale, P. Ao, A. Kazlauskas, and A. L. Boynton Disruption of Gap Junctional Communication by the Platelet-derived Growth Factor Is Mediated via Multiple Signaling Pathways J. Biol. Chem., April 9, 1999; 274(15): 10489 - 10496. [Abstract] [Full Text] [PDF]
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R. van der Voort, T. E. I. Taher, V. J. M. Wielenga, M. Spaargaren, R. Prevo, L. Smit, G. David, G. Hartmann, E. Gherardi, and S. T. Pals Heparan Sulfate-modified CD44 Promotes Hepatocyte Growth Factor/Scatter Factor-induced Signal Transduction through the Receptor Tyrosine Kinase c-Met J. Biol. Chem., March 5, 1999; 274(10): 6499 - 6506. [Abstract] [Full Text] [PDF]
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R. Contreras, L Shoshani, C Flores-Maldonado, A Lazaro, and M Cereijido Relationship between Na(+),K(+)-ATPase and cell attachment J. Cell Sci., January 12, 1999; 112(23): 4223 - 4232. [Abstract] [PDF]
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E. E. Sander, S. van Delft, J. P. ten Klooster, T. Reid, R. A. van der Kammen, F. Michiels, and J. G. Collard Matrix-dependent Tiam1/Rac Signaling in Epithelial Cells Promotes Either Cell-Cell Adhesion or Cell Migration and Is Regulated by Phosphatidylinositol 3-Kinase J. Cell Biol., November 30, 1998; 143(5): 1385 - 1398. [Abstract] [Full Text] [PDF]
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A. Chausovsky, I. Tsarfaty, Z. Kam, Y. Yarden, B. Geiger, and A. D. Bershadsky Morphogenetic Effects of Neuregulin (Neu Differentiation Factor) in Cultured Epithelial Cells Mol. Biol. Cell, November 1, 1998; 9(11): 3195 - 3209. [Abstract] [Full Text]
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F. Galbiati, D. Volonte', A. M. C. Brown, D. E. Weinstein, A. Ben-Ze'ev, R. G. Pestell, and M. P. Lisanti Caveolin-1 Expression Inhibits Wnt/beta -Catenin/Lef-1 Signaling by Recruiting beta -Catenin to Caveolae Membrane Domains J. Biol. Chem., July 21, 2000; 275(30): 23368 - 23377. [Abstract] [Full Text] [PDF]
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Y. Kawano, I. Okamoto, D. Murakami, H. Itoh, M. Yoshida, S. Ueda, and H. Saya Ras Oncoprotein Induces CD44 Cleavage through Phosphoinositide 3-OH Kinase and the Rho Family of Small G Proteins J. Biol. Chem., September 15, 2000; 275(38): 29628 - 29635. [Abstract] [Full Text] [PDF]
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C.-C. Liang and H.-C. Chen Sustained Activation of Extracellular Signal-regulated Kinase Stimulated by Hepatocyte Growth Factor Leads to Integrin alpha 2 Expression That Is Involved in Cell Scattering J. Biol. Chem., June 8, 2001; 276(24): 21146 - 21152. [Abstract] [Full Text] [PDF]
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F. Hollande, A. Choquet, E. M. Blanc, D. J. Lee, J.-P. Bali, and G. S. Baldwin Involvement of Phosphatidylinositol 3-Kinase and Mitogen-activated Protein Kinases in Glycine-extended Gastrin-induced Dissociation and Migration of Gastric Epithelial Cells J. Biol. Chem., October 26, 2001; 276(44): 40402 - 40410. [Abstract] [Full Text] [PDF]
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S. Liu, M. Slepak, and M. H. Ginsberg Binding of Paxillin to the alpha 9 Integrin Cytoplasmic Domain Inhibits Cell Spreading J. Biol. Chem., September 28, 2001; 276(40): 37086 - 37092. [Abstract] [Full Text] [PDF]
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E. Janda, K. Lehmann, I. Killisch, M. Jechlinger, M. Herzig, J. Downward, H. Beug, and S. Grunert Ras and TGF{beta} cooperatively regulate epithelial cell plasticity and metastasis: dissection of Ras signaling pathways J. Cell Biol., January 21, 2002; 156(2): 299 - 314. [Abstract] [Full Text] [PDF]
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G. Pawlak and D. M. Helfman Post-transcriptional Down-regulation of ROCKI/Rho-kinase through an MEK-dependent Pathway Leads to Cytoskeleton Disruption in Ras-transformed Fibroblasts Mol. Biol. Cell, January 1, 2002; 13(1): 336 - 347. [Abstract] [Full Text] [PDF]
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