Cell Biochemistry and Biophysics

, Volume 53, Issue 3, pp 115–126 | Cite as

The Role of Vinculin in the Regulation of the Mechanical Properties of Cells

  • Claudia Tanja Mierke
Original Paper


Vinculin couples as a focal adhesion protein the extracellular matrix (ECM) through integrins to the actomyosin cytoskeleton. During the last years vinculin has become the focus of cell mechanical measurements and a key protein regulating the transmission of contractile forces. In earlier reports vinculin has been described as an inhibitor of cell migration on planar substrates, because knock-out of vinculin in F9 mouse embryonic carcinoma cells and mouse embryonic fibroblasts showed increased cell motility on 2D substrates. The role of vinculin in cell invasion through a 3D extracellular matrix is still fragmentarily investigated. This review presents vinculin in its role as a regulator of cellular mechanical functions. Contractile force generation is reduced when vinculin is absent, or enhanced when vinculin is present. Moreover, the generation of contractile forces is a prerequisite for cell invasion through a dense 3D ECM, where the pore-size is smaller than the diameter of the cell nucleus (<2 μm). Measurements of cell’s biophysical properties will be presented. In summary, vinculin’s leading role among focal adhesion proteins in regulating the mechanical properties of cells will be discussed.


Cytoskeleton Focal adhesions Contractile forces Integrins Vinculin Cell tractions 



This work was supported by the Deutsche Krebshilfe (107384) and the DFG (FA336/2-1).


  1. 1.
    Janmey, P. A., & Weitz, D. A. (2004). Dealing with mechanics: Mechanisms of force transduction in cells. Trends in Biochemical Sciences, 29, 364–370.PubMedGoogle Scholar
  2. 2.
    Discher, D. E., Janmey, P., & Wang, Y. L. (2005). Tissue cells feel and respond to the stiffness of their substrate. Science, 310, 1139–1143.PubMedGoogle Scholar
  3. 3.
    Mierke, C. T., Kollmannsberger, P., Paranhos-Zitterbart, D., Smith, J., Fabry, B., & Goldmann, W. H. (2008). Mechano-coupling and regulation of contractility by the vinculin tail domain. Biophysical Journal, 94, 661–670.PubMedGoogle Scholar
  4. 4.
    Zhang, X., Jiang, G., Cai, Y., Monkley, S. J., Critchley, D. R., & Sheetz, M. P. (2008). Talin depletion reveals independence of initial cell spreading from integrin activation and traction. Nature Cell Biology (Letters), 10, 1062–1068.Google Scholar
  5. 5.
    del Rio, A., Perez-Jimenez, R., Liu, R., Roca-Cusachs, P., Fernandez, J. M., & Sheetz, M. P. (2009). Stretching single talin rod molecules activates vinculin binding. Science, 323, 638–641.PubMedGoogle Scholar
  6. 6.
    Calderwood, D. A., Yan, B., de Pereda, J. M., Alvarez, B. G., Fujioka, Y., Liddington, R. C., et al. (2002). The phosphotyrosine binding-like domain of talin activates integrins. Journal of Biological Chemistry, 277, 21749–21758.PubMedGoogle Scholar
  7. 7.
    Giancotti, F. G. (2000). Complexity and specificity of integrin signalling. Nature Cell Biology, 2, E13–E14.PubMedGoogle Scholar
  8. 8.
    Goldmann, W. H., Schindl, M., Cardozo, T. J., & Ezzell, R. M. (1995). Motility of vinculin-deficient F9 embryonic carcinoma cells analyzed by video, laser confocal, and reflection interference contrast microscopy. Experimental Cell Research, 221, 311–319.PubMedGoogle Scholar
  9. 9.
    Bakolitsa, C., Cohen, D. M., Bankston, L. A., Bobkov, A. A., Cadwell, G. W., Jennings, L., et al. (2004). Structural basis for vinculin activation at sites of cell adhesion. Nature, 430, 583–586.PubMedGoogle Scholar
  10. 10.
    Borgon, R. A., Vonrhein, C., Bricogne, G., Bois, P. R., & Izard, T. (2004). Crystal structure of human vinculin. Structure (Cambridge), 12, 1189–1197.Google Scholar
  11. 11.
    Izard, T., Evans, G., Borgon, R. A., Rush, C. L., Bricogne, G., & Bois, P. R. (2004). Vinculin activation by talin through helical bundle conversion. Nature, 427, 171–175.PubMedGoogle Scholar
  12. 12.
    Bois, P. R., O’Hara, B. P., Nietlispach, D., Kirkpatrick, J., & Izard, T. (2006). The vinculin binding sites of talin and alpha-actinin are sufficient to activate vinculin. Journal of Biological Chemistry, 281, 7228–7236.PubMedGoogle Scholar
  13. 13.
    Wood, C. K., Turner, C. E., Jackson, P., & Critchley, D. R. (1994). Characterisation of the paxillin-binding site and the C-terminal focal adhesion targeting sequence in vinculin. Journal of Cell Science, 107(Pt 2), 709–717.PubMedGoogle Scholar
  14. 14.
    Ziegler, W. H., Liddington, R. C., & Critchley, D. R. (2006). The structure and regulation of vinculin. Trends in Cell Biology, 16, 453–460.PubMedGoogle Scholar
  15. 15.
    Chen, H., Choudhury, D. M., & Craig, S. W. (2006). Coincidence of actin filaments and talin is required to activate vinculin. Journal of Biological Chemistry, 281, 40389–40398.PubMedGoogle Scholar
  16. 16.
    Weekes, J., Barry, S. T., & Critchley, D. R. (1996). Acidic phospholipids inhibit the intramolecular association between the N- and C-terminal regions of vinculin, exposing actin-binding and protein kinase C phosphorylation sites. Biochemical Journal, 314(Pt 3), 827–832.PubMedGoogle Scholar
  17. 17.
    Huttelmaier, S., Mayboroda, O., Harbeck, B., Jarchau, T., Jockusch, B. M., & Rudiger, M. (1998). The interaction of the cell-contact proteins VASP and vinculin is regulated by phosphatidylinositol-4, 5-bisphosphate. Current Biology, 8, 479–488.PubMedGoogle Scholar
  18. 18.
    Cohen, D. M., Kutscher, B., Chen, H., Murphy, D. B., & Craig, S. W. (2006). A conformational switch in vinculin drives formation and dynamics of a talin–vinculin complex at focal adhesions. Journal of Biological Chemistry, 281, 16006–16015.PubMedGoogle Scholar
  19. 19.
    Chen, Y., & Dokholyan, N. V. (2006). Insights into allosteric control of vinculin function from its large scale conformational dynamics. Journal of Biological Chemistry, 281, 29148–29154.PubMedGoogle Scholar
  20. 20.
    Nhieu, G. T., & Izard, T. (2007). Vinculin binding in its closed conformation by a helix addition mechanism. EMBO Journal, 26, 4588–4596.PubMedGoogle Scholar
  21. 21.
    Hytonen, V. P., & Vogel, V. (2008). How force might activate talin’s vinculin binding sites: SMD reveals a structural mechanism. PLoS Computational Biology, 4, e24.PubMedGoogle Scholar
  22. 22.
    Chen, H., Cohen, D. M., Choudhury, D. M., Kioka, N., & Craig, S. W. (2005). Spatial distribution and functional significance of activated vinculin in living cells. Journal of Cell Biology, 169, 459–470.PubMedGoogle Scholar
  23. 23.
    Demali, K. A. (2004). Vinculin—a dynamic regulator of cell adhesion. Trends in Biochemical Sciences, 29, 565–567.PubMedGoogle Scholar
  24. 24.
    Subauste, M. C., Pertz, O., Adamson, E. D., Turner, C. E., Junger, S., & Hahn, K. M. (2004). Vinculin modulation of paxillin–FAK interactions regulates ERK to control survival and motility. Journal of Cell Biology, 165, 371–381.PubMedGoogle Scholar
  25. 25.
    Geiger, B., Tokuyasu, K. T., Dutton, A. H., & Singer, S. J. (1980). Vinculin, an intracellular protein localized at specialized sites where microfilament bundles terminate at cell membranes. Proceedings of the National Academy of Sciences of the United States of America, 77, 4127–4131.PubMedGoogle Scholar
  26. 26.
    Volberg, T., Geiger, B., Kam, Z., Pankov, R., Simcha, I., Sabanay, H., et al. (1995). Focal adhesion formation by F9 embryonal carcinoma cells after vinculin gene disruption. Journal of Cell Science, 108(Pt 6), 2253–2260.PubMedGoogle Scholar
  27. 27.
    Goldmann, W. H., Ezzell, R. M., Adamson, E. D., Niggli, V., & Isenberg, G. (1996). Vinculin, talin and focal adhesions. Journal of Muscle Research and Cell Motility, 17, 1–5.PubMedGoogle Scholar
  28. 28.
    Goldmann, W. H. (2000). Kinetic determination of focal adhesion protein formation. Biochemical and Biophysical Research Communications, 271, 553–557.PubMedGoogle Scholar
  29. 29.
    Turner, C. E. (1998). Paxillin. International Journal of Biochemistry and Cell Biology, 30, 955–959.PubMedGoogle Scholar
  30. 30.
    Geiger, B., & Ginsberg, D. (1991). The cytoplasmic domain of adherens-type junctions. Cell Motility and the Cytoskeleton, 20, 1–6.PubMedGoogle Scholar
  31. 31.
    Turner, C. E., & Burridge, K. (1991). Transmembrane molecular assemblies in cell-extracellular matrix interactions. Current Opinion in Cell Biology, 3, 849–853.PubMedGoogle Scholar
  32. 32.
    Kioka, N., Sakata, S., Kawauchi, T., Amachi, T., Akiyama, S. K., Okazaki, K., et al. (1999). Vinexin: A novel vinculin-binding protein with multiple SH3 domains enhances actin cytoskeletal organization. Journal of Cell Biology, 144, 59–69.PubMedGoogle Scholar
  33. 33.
    Geiger, B., Bershadsky, A., Pankov, R., & Yamada, K. M. (2001). Transmembrane crosstalk between the extracellular matrix–cytoskeleton crosstalk. Nature Reviews. Molecular Cell Biology, 2, 793–805.PubMedGoogle Scholar
  34. 34.
    Johnson, R. P., Niggli, V., Durrer, P., & Craig, S. W. (1998). A conserved motif in the tail domain of vinculin mediates association with and insertion into acidic phospholipid bilayers. Biochemistry, 37, 10211–10222.PubMedGoogle Scholar
  35. 35.
    Diez, G., List, F., Smith, J., Ziegler, W. H., & Goldmann, W. H. (2008). Direct evidence of vinculin tail–lipid membrane interaction in beta-sheet conformation. Biochemical and Biophysical Research Communications, 373, 69–73.PubMedGoogle Scholar
  36. 36.
    Steimle, P. A., Hoffert, J. D., Adey, N. B., & Craig, S. W. (1999). Polyphosphoinositides inhibit the interaction of vinculin with actin filaments. Journal of Biological Chemistry, 274, 18414–18420.PubMedGoogle Scholar
  37. 37.
    Barstead, R. J., & Waterston, R. H. (1989). The basal component of the nematode dense-body is vinculin. Journal of Biological Chemistry, 264, 10177–10185.PubMedGoogle Scholar
  38. 38.
    Saez, A. O., Zhang, W., Wu, Y., Turner, C. E., Tang, D. D., & Gunst, S. J. (2004). Tension development during contractile stimulation of smooth muscle requires recruitment of paxillin and vinculin to the membrane. American Journal of Physiology. Cell Physiology, 286, C433–C447.Google Scholar
  39. 39.
    Xu, W., Baribault, H., & Adamson, E. D. (1998). Vinculin knockout results in heart and brain defects during embryonic development. Development, 125, 327–337.PubMedGoogle Scholar
  40. 40.
    Zemljic-Harpf, A. E., Ponrartana, S., Avalos, R. T., Jordan, M. C., Roos, K. P., Dalton, N. D., et al. (2004). Heterozygous inactivation of the vinculin gene predisposes to stress-induced cardiomyopathy. American Journal of Pathology, 165, 1033–1044.PubMedGoogle Scholar
  41. 41.
    Rodriguez Fernandez, J. L., Geiger, B., Salomon, D., & Ben-Ze’ev, A. (1993). Suppression of vinculin expression by antisense transfection confers changes in cell morphology, motility, and anchorage-dependent growth of 3T3 cells. Journal of Cell Biology, 122, 1285–1294.PubMedGoogle Scholar
  42. 42.
    Xu, W., Coll, J. L., & Adamson, E. D. (1998). Rescue of the mutant phenotype by reexpression of full-length vinculin in null F9 cells; effects on cell locomotion by domain deleted vinculin. Journal of Cell Science, 111(Pt 11), 1535–1544.PubMedGoogle Scholar
  43. 43.
    Rodriguez Fernandez, J. L., Geiger, B., Salomon, D., Sabanay, I., Zoller, M., & Ben-Ze’ev, A. (1992). Suppression of tumorigenicity in transformed cells after transfection with vinculin cDNA. Journal of Cell Biology, 119, 427–438.PubMedGoogle Scholar
  44. 44.
    Subauste, M. C., Nalbant, P., Adamson, E. D., & Hahn, K. M. (2004). Vinculin controls PTEN protein level by maintaining the interaction of the adherens junction protein b-catenin with the scaffolding protein membrane associated guanylate kinase inverted-2 (MAGI-2). Journal of Biological Chemistry, 280, 5676.PubMedGoogle Scholar
  45. 45.
    Bershadsky, A. D., Gluck, U., Denisenko, O. N., Sklyarova, T. V., Spector, I., & Ben-Ze’ev, A. (1995). The state of actin assembly regulates actin and vinculin expression by a feedback loop. Journal of Cell Science, 108(Pt 3), 1183–1193.PubMedGoogle Scholar
  46. 46.
    Rottner, K., Hall, A., & Small, J. V. (1999). Interplay between Rac and Rho in the control of substrate contact dynamics. Current Biology, 9, 640–648.PubMedGoogle Scholar
  47. 47.
    Zamir, E., Katz, M., Posen, Y., Erez, N., Yamada, K. M., Katz, B. Z., et al. (2000). Dynamics and segregation of cell-matrix adhesions in cultured fibroblasts. Nature Cell Biology, 2, 191–196.PubMedGoogle Scholar
  48. 48.
    Zamir, E., Katz, B. Z., Aota, S., Yamada, K. M., Geiger, B., & Kam, Z. (1999). Molecular diversity of cell–matrix adhesions. Journal of Cell Science, 112(Pt 11), 1655–1669.PubMedGoogle Scholar
  49. 49.
    Katz, B. Z., Zamir, E., Bershadsky, A., Kam, Z., Yamada, K. M., & Geiger, B. (2000). Physical state of the extracellular matrix regulates the structure and molecular composition of cell–matrix adhesions. Molecular Biology of the Cell, 11, 1047–1060.PubMedGoogle Scholar
  50. 50.
    Webb, D. J., Donais, K., Whitmore, L. A., Thomas, S. M., Turner, C. E., Parsons, J. T., et al. (2004). FAK–Src signalling through paxillin, ERK, and MLCK regulates adhesion disassembly. Nature Cell Biology, 6, 154–161.PubMedGoogle Scholar
  51. 51.
    Friedl, P., & Brocker, E. B. (2000). The biology of cell locomotion within three-dimensional extracellular matrix. Cellular and Molecular Life Sciences, 57, 41–64.PubMedGoogle Scholar
  52. 52.
    Mierke, C. T., Rosel, D., Fabry, B., & Brabek, J. (2008). Contractile forces in tumor cell migration. European Journal of Cell Biology, 87, 669–676.PubMedGoogle Scholar
  53. 53.
    Zaman, M. H., Trapani, L. M., Siemeski, A., Mackellar, D., Gong, H., Kamm, R. D., et al. (2006). Migration of tumor cells in 3D matrices is governed by matrix stiffness along with cell–matrix adhesion and proteolysis. Proceedings of the National Academy of Sciences of the United States of America, 103, 10889–10894.PubMedGoogle Scholar
  54. 54.
    Wolf, K., Mazo, I., Leung, H., Engelke, K., von Andrian, U. H., Deryugina, E. I., et al. (2003). Compensation mechanism in tumor cell migration: Mesenchymal–amoeboid transition after blocking of pericellular proteolysis. Journal of Cell Biology, 160, 267–277.PubMedGoogle Scholar
  55. 55.
    Wolf, K., Wu, Y. I., Liu, Y., Geiger, J., Tam, E., Overall, C., et al. (2007). Multi-step pericellular proteolysis controls the transition from individual to collective cancer cell invasion. Nature Cell Biology, 9, 893–904.PubMedGoogle Scholar
  56. 56.
    Friedl, P., & Wolf, K. (2009). Proteolytic interstitial cell migration: A five-step process. Cancer Metastasis Reviews, 28, 129–135.PubMedGoogle Scholar
  57. 57.
    Li, X. Y., Ota, I., Yana, I., Sabeh, F., & Weiss, S. J. (2008). Molecular dissection of the structural machinery underlying the tissue-invasive activity of membrane type-1 matrix metalloproteinase. Molecular Biology of the Cell, 19, 3221–3233.PubMedGoogle Scholar
  58. 58.
    Itoh, Y., Ito, N., Nagase, H., & Seiki, M. (2008). The second dimer interface of MT1-MMP, the transmembrane domain, is essential for ProMMP-2 activation on the cell surface. Journal of Biological Chemistry, 283, 13053–13062.PubMedGoogle Scholar
  59. 59.
    Mierke, C. T., Zitterbart, D. P., Kollmannsberger, P., Raupach, C., Schlotzer-Schrehardt, U., Goecke, T. W., et al. (2008). Breakdown of the endothelial barrier function in tumor cell transmigration. Biophysical Journal, 94, 2832–2846.PubMedGoogle Scholar
  60. 60.
    Rosel, D., Brabek, J., Tolde, O., Mierke, C. T., Zitterbart, D. P., Raupach, C., et al. (2008). Up-regulation of Rho/ROCK Signaling in Sarcoma Cells Drives Invasion and Increased Generation of Protrusive Forces. Molecular Cancer Research, 6, 1410–1420.PubMedGoogle Scholar
  61. 61.
    Bloom, R.J., George, J.P., Celedon, A., Sun, S.X., & Wirtz, D. (2008). Mapping local matrix remodeling induced by a migrating tumor cell using 3-D multiple-particle tracking. Biophysical Journal, 95, 4077–4088.Google Scholar
  62. 62.
    Leung, L. Y., Tian, D., Brangwynne, C. P., Weitz, D. A., & Tschumperlin, D. J. (2007). A new microrheometric approach reveals individual and cooperative roles for TGF-beta1 and IL-1beta in fibroblast-mediated stiffening of collagen gels. FASEB Journal, 21, 1–10.Google Scholar
  63. 63.
    Wang, N., Butler, J. P., & Ingber, D. E. (1993). Mechanotransduction across the cell surface and through the cytoskeleton. Science, 260, 1124–1127.PubMedGoogle Scholar
  64. 64.
    Neff, N. T., Lowrey, C., Decker, C., Tovar, A., Damsky, C., Buck, C., et al. (1982). A monoclonal antibody detaches embryonic skeletal muscle from extracellular matrices. Journal of Cell Biology, 95, 654–666.PubMedGoogle Scholar
  65. 65.
    Damsky, C. H., Knudsen, K. A., Bradley, D., Buck, C. A., & Horwitz, A. F. (1985). Distribution of the cell substratum attachment (CSAT) antigen on myogenic and fibroblastic cells in culture. Journal of Cell Biology, 100, 1528–1539.PubMedGoogle Scholar
  66. 66.
    Palecek, S. P., Loftus, J. C., Ginsberg, M. H., Lauffenburger, D. A., & Horwitz, A. F. (1997). Integrin–ligand binding properties govern cell migration speed through cell–substratum adhesiveness. Nature, 385, 537–540.PubMedGoogle Scholar
  67. 67.
    Loftus, J. C., & Liddington, R. C. (1997). Cell adhesion in vascular biology. New insights into integrin-ligand interaction. The Journal of Clinical Investigation, 99, 2302–2306.PubMedGoogle Scholar
  68. 68.
    Humphries, J. D., Wang, P., Streuli, C., Geiger, B., Humphries, M. J., & Ballestrem, C. (2007). Vinculin controls focal adhesion formation by direct interactions with talin and actin. Journal of Cell Biology, 179, 1043–1057.PubMedGoogle Scholar
  69. 69.
    Liu, S., & Ginsberg, M. H. (2000). Paxillin binding to a conserved sequence motif in the alpha 4 integrin cytoplasmic domain. Journal of Biological Chemistry, 275, 22736–22742.PubMedGoogle Scholar
  70. 70.
    Young, B. A., Taooka, Y., Liu, S., Askins, K. J., Yokosaki, Y., Thomas, S. M., et al. (2001). The cytoplasmic domain of the integrin alpha9 subunit requires the adaptor protein paxillin to inhibit cell spreading but promotes cell migration in a paxillin-independent manner. Molecular Biology of the Cell, 12, 3214–3225.PubMedGoogle Scholar
  71. 71.
    Liu, S., Slepak, M., & Ginsberg, M. H. (2001). Binding of paxillin to the alpha 9 integrin cytoplasmic domain inhibits cell spreading. Journal of Biological Chemistry, 276, 37086–37092.PubMedGoogle Scholar
  72. 72.
    Horwitz, A. R., & Parsons, J. T. (1999). Cell migration–movin’ on. Science, 286, 1102–1103.PubMedGoogle Scholar
  73. 73.
    Rolli, M., Fransvea, E., Pilch, J., Saven, A., & Felding-Habermann, B. (2003). Activated integrin alphavbeta3 cooperates with metalloproteinase MMP-9 in regulating migration of metastatic breast cancer cells. Proceedings of the National Academy of Sciences of the United States of America, 100, 9482–9487.PubMedGoogle Scholar
  74. 74.
    Schmid, R. S., Shelton, S., Stanco, A., Yokota, Y., Kreidberg, J. A., & Anton, E. S. (2004). Alpha3beta1 integrin modulates neuronal migration and placement during early stages of cerebral cortical development. Development, 131, 6023–6031.PubMedGoogle Scholar
  75. 75.
    Pawar, S. C., Demetriou, M. C., Nagle, R. B., Bowden, G. T., & Cress, A. E. (2007). Integrin alpha6 cleavage: A novel modification to modulate cell migration. Experimental Cell Research, 313, 1080–1089.PubMedGoogle Scholar
  76. 76.
    Rout, U. K., Wang, J., Paria, B. C., & Armant, D. R. (2004). Alpha5beta1, alphaVbeta3 and the platelet-associated integrin alphaIIbbeta3 coordinately regulate adhesion and migration of differentiating mouse trophoblast cells. Developmental Biology, 268, 135–151.PubMedGoogle Scholar
  77. 77.
    Hu, D. D., Hoyer, J. R., & Smith, J. W. (1995). Ca2+ suppresses cell adhesion to osteopontin by attenuating binding affinity for integrin alpha v beta 3. Journal of Biological Chemistry, 270, 9917–9925.PubMedGoogle Scholar
  78. 78.
    Liaw, L., Lindner, V., Schwartz, S. M., Chambers, A. F., & Giachelli, C. M. (1995). Osteopontin and beta 3 integrin are coordinately expressed in regenerating endothelium in vivo and stimulate Arg-Gly-Asp-dependent endothelial migration in vitro. Circulation Research, 77, 665–672.PubMedGoogle Scholar
  79. 79.
    Miyauchi, A., Alvarez, J., Greenfield, E. M., Teti, A., Grano, M., Colucci, S., et al. (1991). Recognition of osteopontin and related peptides by an alpha v beta 3 integrin stimulates immediate cell signals in osteoclasts. Journal of Biological Chemistry, 266, 20369–20374.PubMedGoogle Scholar
  80. 80.
    Barry, S. T., Ludbrook, S. B., Murrison, E., & Horgan, C. M. (2000). Analysis of the alpha4beta1 integrin-osteopontin interaction. Experimental Cell Research, 258, 342–351.PubMedGoogle Scholar
  81. 81.
    Nasu, K., Ishida, T., Setoguchi, M., Higuchi, Y., Akizuki, S., & Yamamoto, S. (1995). Expression of wild-type and mutated rabbit osteopontin in Escherichia coli, and their effects on adhesion and migration of P388D1 cells. Biochemical Journal, 307(Pt 1), 257–265.PubMedGoogle Scholar
  82. 82.
    Ly, D. P., Zazzali, K. M., & Corbett, S. A. (2003). De novo expression of the integrin alpha5beta1 regulates alphavbeta3-mediated adhesion and migration on fibrinogen. Journal of Biological Chemistry, 278, 21878–21885.PubMedGoogle Scholar
  83. 83.
    Qian, F., Zhang, Z. C., Wu, X. F., Li, Y. P., & Xu, Q. (2005). Interaction between integrin alpha(5) and fibronectin is required for metastasis of B16F10 melanoma cells. Biochemical and Biophysical Research Communications, 333, 1269–1275.PubMedGoogle Scholar
  84. 84.
    Sawada, K., Mitra, A. K., Radjabi, A. R., Bhaskar, V., Kistner, E. O., Tretiakova, M., et al. (2008). Loss of E-cadherin promotes ovarian cancer metastasis via alpha 5-integrin, which is a therapeutic target. Cancer Research, 68, 2329–2339.PubMedGoogle Scholar
  85. 85.
    Taverna, D., Ullman-Cullere, M., Rayburn, H., Bronson, R. T., & Hynes, R. O. (1998). A test of the role of alpha5 integrin/fibronectin interactions in tumorigenesis. Cancer Research, 58, 848–853.PubMedGoogle Scholar
  86. 86.
    Schirner, M., Herzberg, F., Schmidt, R., Streit, M., Schoning, M., Hummel, M., et al. (1998). Integrin alpha5beta1: A potent inhibitor of experimental lung metastasis. Clinical & Experimental Metastasis, 16, 427–435.Google Scholar
  87. 87.
    Tani, N., Higashiyama, S., Kawaguchi, N., Madarame, J., Ota, I., Ito, Y., et al. (2003). Expression level of integrin alpha 5 on tumour cells affects the rate of metastasis to the kidney. British Journal of Cancer, 88, 327–333.PubMedGoogle Scholar
  88. 88.
    Havaki, S., Kouloukoussa, M., Amawi, K., Drosos, Y., Arvanitis, L. D., Goutas, N., et al. (2007). Altered expression pattern of integrin alphavbeta3 correlates with actin cytoskeleton in primary cultures of human breast cancer. Cancer Cell International, 7, 16.PubMedGoogle Scholar
  89. 89.
    Felding-Habermann, B., O’Toole, T. E., Smith, J. W., Fransvea, E., Ruggeri, Z. M., Ginsberg, M. H., et al. (2001). Integrin activation controls metastasis in human breast cancer. Proceedings of the National Academy of Sciences of the United States of America, 98, 1853–1858.PubMedGoogle Scholar
  90. 90.
    Nystrom, M. L., McCulloch, D., Weinreb, P. H., Violette, S. M., Speight, P. M., Marshall, J. F., et al. (2006). Cyclooxygenase-2 inhibition suppresses alphavbeta6 integrin-dependent oral squamous carcinoma invasion. Cancer Research, 66, 10833–10842.PubMedGoogle Scholar
  91. 91.
    Chung, J., Yoon, S. O., Lipscomb, E. A., & Mercurio, A. M. (2004). The Met receptor and alpha 6 beta 4 integrin can function independently to promote carcinoma invasion. Journal of Biological Chemistry, 279, 32287–32293.PubMedGoogle Scholar
  92. 92.
    Hong, T., & Grabel, L. B. (2006). Migration of F9 parietal endoderm cells is regulated by the ERK pathway. Journal of Cellular Biochemistry, 97, 1339–1349.PubMedGoogle Scholar
  93. 93.
    Turner, C. E., Brown, M. C., Perrotta, J. A., Riedy, M. C., Nikolopoulos, S. N., McDonald, A. R., et al. (1999). Paxillin LD4 motif binds PAK and PIX through a novel 95-kD ankyrin repeat, ARF-GAP protein: A role in cytoskeletal remodeling. Journal of Cell Biology, 145, 851–863.PubMedGoogle Scholar
  94. 94.
    Klemke, R. L., Cai, S., Giannini, A. L., Gallagher, P. J., de Lanerolle, P., & Cheresh, D. A. (1997). Regulation of cell motility by mitogen-activated protein kinase. Journal of Cell Biology, 137, 481–492.PubMedGoogle Scholar
  95. 95.
    Sanders, L. C., Matsumura, F., Bokoch, G. M., & de Lanerolle, P. (1999). Inhibition of myosin light chain kinase by p21-activated kinase. Science, 283, 2083–2085.PubMedGoogle Scholar
  96. 96.
    Balaban, N. Q., Schwarz, U. S., Riveline, D., Goichberg, P., Tzur, G., Sabanay, I., et al. (2001). Force and focal adhesion assembly: A close relationship studied using elastic micropatterned substrates. Nature Cell Biology, 3, 466–472.PubMedGoogle Scholar
  97. 97.
    Riveline, D., Zamir, E., Balaban, N. Q., Schwarz, U. S., Ishizaki, T., Narumiya, S., et al. (2001). Focal contacts as mechanosensors: Externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism. Journal of Cell Biology, 153, 1175–1186.PubMedGoogle Scholar
  98. 98.
    Alenghat, F. J., & Ingber, D. E. (2002). Mechanotransduction: All signals point to cytoskeleton, matrix, and integrins. Science’s STKE, 2002, PE6.PubMedGoogle Scholar
  99. 99.
    Geiger, B., & Bershadsky, A. (2002). Exploring the neighborhood: Adhesion-coupled cell mechanosensors. Cell, 110, 139–142.PubMedGoogle Scholar
  100. 100.
    Chen, C. S., Tan, J., & Tien, J. (2004). Mechanotransduction at cell–matrix and cell–cell contacts. Annual Review of Biomedical Engineering, 6, 275–302.PubMedGoogle Scholar
  101. 101.
    Vogel, V., & Sheetz, M. (2006). Local force and geometry sensing regulate cell functions. Nature Reviews. Molecular Cell Biology, 7, 265–275.PubMedGoogle Scholar
  102. 102.
    Ezzell, R. M., Goldmann, W. H., Wang, N., Parasharama, N., & Ingber, D. E. (1997). Vinculin promotes cell spreading by mechanically coupling integrins to the cytoskeleton. Experimental Cell Research, 231, 14–26.PubMedGoogle Scholar
  103. 103.
    Ling, K., Doughman, R. L., Firestone, A. J., Bunce, M. W., & Anderson, R. A. (2002). Type I gamma phosphatidylinositol phosphate kinase targets and regulates focal adhesions. Nature, 420, 89–93.PubMedGoogle Scholar
  104. 104.
    Chandrasekar, I., Stradal, T. E., Holt, M. R., Entschladen, F., Jockusch, B. M., & Ziegler, W. H. (2005). Vinculin acts as a sensor in lipid regulation of adhesion-site turnover. Journal of Cell Science, 118, 1461–1472.PubMedGoogle Scholar
  105. 105.
    Goldmann, W. H., & Ingber, D. E. (2002). Intact vinculin protein is required for control of cell shape, cell mechanics, and rac-dependent lamellipodia formation. Biochemical and Biophysical Research Communications, 290, 749–755.PubMedGoogle Scholar
  106. 106.
    Goldmann, W. H., Galneder, R., Ludwig, M., Xu, W., Adamson, E. D., Wang, N., et al. (1998). Differences in elasticity of vinculin-deficient F9 cells measured by magnetometry and atomic force microscopy. Experimental Cell Research, 239, 235–242.PubMedGoogle Scholar
  107. 107.
    Goldmann, W. H., & Ezzell, R. M. (1996). Viscoelasticity in wild-type and vinculin-deficient (5.51) mouse F9 embryonic carcinoma cells examined by atomic force microscopy and rheology. Experimental Cell Research, 226, 234–237.PubMedGoogle Scholar
  108. 108.
    Alenghat, F. J., Fabry, B., Tsai, K. Y., Goldmann, W. H., & Ingber, D. E. (2000). Analysis of cell mechanics in single vinculin-deficient cells using a magnetic tweezer. Biochemical and Biophysical Research Communications, 277, 93–99.PubMedGoogle Scholar
  109. 109.
    Harris, A. K., Wild, P., & Stopak, D. (1980). Silicone rubber substrata: A new wrinkle in the study of cell locomotion. Science, 208, 177–179.PubMedGoogle Scholar
  110. 110.
    Pelham, R. J., Jr., & Wang, Y. (1997). Cell locomotion and focal adhesions are regulated by substrate flexibility. Proceedings of the National Academy of Sciences of the United States of America, 94, 13661–13665.PubMedGoogle Scholar
  111. 111.
    Dembo, M., & Wang, Y. L. (1999). Stresses at the cell-to-substrate interface during locomotion of fibroblasts. Biophysical Journal, 76, 2307–2316.PubMedGoogle Scholar
  112. 112.
    Butler, J. P., Tolic-Norrelykke, I. M., Fabry, B., & Fredberg, J. J. (2002). Traction fields, moments, and strain energy that cells exert on their surroundings. American Journal of Physiology. Cell Physiology, 282, C595–C605.PubMedGoogle Scholar
  113. 113.
    Sabass, B., Gardel, M. L., Waterman, C. M., & Schwarz, U. S. (2007). High resolution traction force microscopy based on experimental and computational advances. Biophysical Journal, 94, 207–220.PubMedGoogle Scholar
  114. 114.
    Raupach, C., Zitterbart, D. P., Mierke, C. T., Metzner, C., Muller, F. A., & Fabry, B. (2007). Stress fluctuations and motion of cytoskeletal-bound markers. Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics, 76, 011918.PubMedGoogle Scholar
  115. 115.
    Frixen, U. H., Behrens, J., Sachs, M., Eberle, G., Voss, B., Warda, A., et al. (1991). E-cadherin-mediated cell–cell adhesion prevents invasiveness of human carcinoma cells. Journal of Cell Biology, 113, 173–185.PubMedGoogle Scholar
  116. 116.
    Batlle, E., Sancho, E., Franci, C., Dominguez, D., Monfar, M., Baulida, J., et al. (2000). The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nature Cell Biology, 2, 84–89.PubMedGoogle Scholar
  117. 117.
    Cano, A., Perez-Moreno, M. A., Rodrigo, I., Locascio, A., Blanco, M. J., del Barrio, M. G., et al. (2000). The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nature Cell Biology, 2, 76–83.PubMedGoogle Scholar
  118. 118.
    De Craene, B., Gilbert, B., Stove, C., Bruyneel, E., van Roy, F., & Berx, G. (2005). The transcription factor snail induces tumor cell invasion through modulation of the epithelial cell differentiation program. Cancer Research, 65, 6237–6244.PubMedGoogle Scholar
  119. 119.
    Steeg, P. S. (2006). Tumor metastasis: Mechanistic insights and clinical challenges. Nature Medicine, 12, 895–904.PubMedGoogle Scholar
  120. 120.
    Al-Mehdi, A. B., Tozawa, K., Fisher, A. B., Shientag, L., Lee, A., & Muschel, R. J. (2000). Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: A new model for metastasis. Nature Medicine, 6, 100–102.PubMedGoogle Scholar
  121. 121.
    Saunders, R. M., Holt, M. R., Jennings, L., Sutton, D. H., Barsukov, I. L., Bobkov, A., et al. (2006). Role of vinculin in regulating focal adhesion turnover. European Journal of Cell Biology, 85, 487–500.PubMedGoogle Scholar
  122. 122.
    Coll, J. L., Ben-Ze’ev, A., Ezzell, R. M., Rodriguez Fernandez, J. L., Baribault, H., Oshima, R. G., et al. (1995). Targeted disruption of vinculin genes in F9 and embryonic stem cells changes cell morphology, adhesion, and locomotion. Proceedings of the National Academy of Sciences of the United States of America, 92, 9161–9165.PubMedGoogle Scholar
  123. 123.
    Raz, A., & Geiger, B. (1982). Altered organization of cell-substrate contacts and membrane-associated cytoskeleton in tumor cell variants exhibiting different metastatic capabilities. Cancer Research, 42, 5183–5190.PubMedGoogle Scholar
  124. 124.
    Lifschitz-Mercer, B., Czernobilsky, B., Feldberg, E., & Geiger, B. (1997). Expression of the adherens junction protein vinculin in human basal and squamous cell tumors: Relationship to invasiveness and metastatic potential. Human Pathology, 28, 1230–1236.PubMedGoogle Scholar
  125. 125.
    Summy, J. M., & Gallick, G. E. (2003). Src family kinases in tumor progression and metastasis. Cancer and Metastasis Reviews, 22, 337–358.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2009

Authors and Affiliations

  1. 1.Center for Medical Physics and Technology, Biophysics GroupFriedrich-Alexander-University of Erlangen-NurembergErlangenGermany

Personalised recommendations