Cancer and Metastasis Reviews

, Volume 29, Issue 1, pp 223–237 | Cite as

Important role of integrins in the cancer biology

NON-THEMATIC REVIEW

Abstract

Adhesion of breast cancer cells is supported by various integrins. Cell adhesion is critical for maintenance of both three-dimensional and normal function of these tissues. Several integrins have been shown to have higher expression levels in metastatic cancers and have been implicated in degrading basement membrane by interacting with proteolytic enzymes. This suggests that a group of integrins plays an important role in migration and invasion through the remodeling of the extracellular matrix. In this review, we highlight recent advances in our understanding of how integrins regulate breast cancer through modulation of the actin cytoskeleton and the mechanisms that regulate this process. Also, we highlight the importance of integrin-binding proteins in cell migration and mechanisms that operate in invasive cells, during breast cancer progression.

Keywords

Integrin Breast cancer Cancer Actin cytoskeleton 

Notes

Acknowledgments

We express sincere apologies to many scientists whose work could not be cited because of space constraints. This works is supported by the National Cancer Institute grant CA 115706, Susan Komen Foundation grant (BCTR 0600278), and Louisiana Board of Regents grant (LEQSF-RD-A-14) and funds from Louisiana Cancer Research Consortium. Also we like to thank our colleagues Wayne Vedeckis, Allison Berrier, and Becky Worthylake for critical reading of the manuscript.

References

  1. 1.
    van der Flier, A., & Sonnenberg, A. (2001). Function and interactions of integrins. Cell and Tissue Research, 305, 285–298.PubMedGoogle Scholar
  2. 2.
    Colombatti, A., Bonaldo, P., & Doliana, R. (1993). Type A modules: Interacting domains found in several non-fibrillar collagens and in other extracellular matrix proteins. Matrix, 13, 297–306.PubMedGoogle Scholar
  3. 3.
    Rosen, P. P., Groshen, S., Saigo, P. E., Kinne, D. W., & Hellman, S. (1989). Pathological prognostic factors in stage I (T1N0M0) and stage II (T1N1M0) breast carcinoma: a study of 644 patients with median follow-up of 18 years. Journal of Clinical Oncology, 7, 1239–1251.PubMedGoogle Scholar
  4. 4.
    Aplin, A. E., Howe, A. K., & Juliano, R. L. (1999). Cell adhesion molecules, signal transduction and cell growth. Current Opinion in Cell Biology, 11, 737–744.PubMedGoogle Scholar
  5. 5.
    Sastry, S. K., & Burridge, K. (2000). Focal adhesions: a nexus for intracellular signaling and cytoskeletal dynamics. Experimental Cell Research, 261, 25–36.PubMedGoogle Scholar
  6. 6.
    Weaver, V. M., Fischer, A. H., Peterson, O. W., & Bissell, M. J. (1996). The importance of the microenvironment in breast cancer progression: Recapitulation of mammary tumorigenesis using a unique human mammary epithelial cell model and a three-dimensional culture assay. Biochemistry and Cell Biology, 74, 833–851.PubMedGoogle Scholar
  7. 7.
    Liapis, H., Flath, A., & Kitazawa, S. (1996). Integrin alpha V beta 3 expression by bone-residing breast cancer metastases. Diagnostic Molecular Pathology, 5, 127–135.PubMedGoogle Scholar
  8. 8.
    Pawelek, J. M., & Chakraborty, A. K. (2008). The cancer cell–leukocyte fusion theory of metastasis. Advances in Cancer Research, 101, 397–444.PubMedGoogle Scholar
  9. 9.
    Aumailley, M., Pesch, M., Tunggal, L., Gaill, F., & Fassler, R. (2000). Altered synthesis of laminin 1 and absence of basement membrane component deposition in (beta)1 integrin-deficient embryoid bodies. Journal of Cell Science, 113(Pt 2), 259–268.PubMedGoogle Scholar
  10. 10.
    Folgiero, V., Bachelder, R. E., Bon, G., Sacchi, A., Falcioni, R., & Mercurio, A. M. (2007). The alpha6beta4 integrin can regulate ErbB-3 expression: implications for alpha6beta4 signaling and function. Cancer Research, 67, 1645–1652.PubMedGoogle Scholar
  11. 11.
    Kim, T. H., Kim, H. I., Soung, Y. H., Shaw, L. A., & Chung, J. (2009). Integrin (alpha6beta4) signals through Src to increase expression of S100A4, a metastasis-promoting factor: implications for cancer cell invasion. Molecular Cancer Res, 7, 1605–1612.Google Scholar
  12. 12.
    Brooks, P. C., Stromblad, S., Sers, L. C., von Schalscha, T. L., Aimes, R. T., Stetler-Stevenson, W. G., et al. (1996). Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3. Cell, 85, 683–693.PubMedGoogle Scholar
  13. 13.
    Deryugina, E. I., Bourdon, M. A., Luo, G. X., Reisfeld, R. A., & Strongin, A. (1997). Matrix metalloproteinase-2 activation modulates glioma cell migration. Journal of Cell Science, 110(Pt 19), 2473–2482.PubMedGoogle Scholar
  14. 14.
    Glinskii, A. B., Glinsky, G. V., Lin, H. Y., Tang, H. Y., Sun, M., Davis, F. B., et al. (2009). Modification of survival pathway gene expression in human breast cancer cells by tetraiodothyroacetic acid (tetrac). Cell Cycle, 8, 3554–3562.PubMedGoogle Scholar
  15. 15.
    Tang, J., Wu, Y. M., Zhao, P., Jiang, J. L., & Chen, Z. N. (2009). Betaig-h3 interacts with alpha3beta1 integrin to promote adhesion and migration of human hepatoma cells. Experimental Biology and Medicine (Maywood), 234, 35–39.Google Scholar
  16. 16.
    Wendt, M. K., & Schiemann, W. P. (2009). Therapeutic targeting of the focal adhesion complex prevents oncogenic TGF-beta signaling and metastasis. Breast Cancer Research, 11, R68.PubMedGoogle Scholar
  17. 17.
    Gomes, N., Vassy, J., Lebos, C., Arbeille, B., Legrand, C., & Fauvel-Lafeve, F. (2004). Breast adenocarcinoma cell adhesion to the vascular subendothelium in whole blood and under flow conditions: effects of alphavbeta3 and alphaIIbbeta3 antagonists. Clinical & Experimental Metastasis, 21, 553–561.Google Scholar
  18. 18.
    Rousselle, P., & Aumailley, M. (1994). Kalinin is more efficient than laminin in promoting adhesion of primary keratinocytes and some other epithelial cells and has a different requirement for integrin receptors. Journal of Cell Biology, 125, 205–214.PubMedGoogle Scholar
  19. 19.
    Kielosto, M., Nummela, P., Jarvinen, K., Yin, M., & Holtta, E. (2009). Identification of integrins alpha6 and beta7 as c-Jun- and transformation-relevant genes in highly invasive fibrosarcoma cells. International Journal of Cancer, 125, 1065–1073.Google Scholar
  20. 20.
    He, Y., Liu, X. D., Chen, Z. Y., Zhu, J., Xiong, Y., Li, K., et al. (2007). Interaction between cancer cells and stromal fibroblasts is required for activation of the uPAR-uPA-MMP-2 cascade in pancreatic cancer metastasis. Clinical Cancer Research, 13, 3115–3124.PubMedGoogle Scholar
  21. 21.
    Desgrosellier, J. S., Barnes, L. A., Shields, D. J., Huang, M., Lau, S. K., Prevost, N., et al. (2009). An integrin alpha(v)beta(3)-c-Src oncogenic unit promotes anchorage-independence and tumor progression. Nature Medicine, 15, 1163–1169.PubMedGoogle Scholar
  22. 22.
    Chen, M., Sinha, M., Luxon, B. A., Bresnick, A. R., & O'Connor, K. L. (2009). Integrin alpha6beta4 controls the expression of genes associated with cell motility, invasion, and metastasis, including S100A4/metastasin. Journal of Biological Chemistry, 284, 1484–1494.PubMedGoogle Scholar
  23. 23.
    O'Connor, K. L., Shaw, L. M., & Mercurio, A. M. (1998). Release of cAMP gating by the alpha6beta4 integrin stimulates lamellae formation and the chemotactic migration of invasive carcinoma cells. Journal of Cell Biology, 143, 1749–1760.PubMedGoogle Scholar
  24. 24.
    Lipscomb, E. A., Dugan, A. S., Rabinovitz, I., & Mercurio, A. M. (2003). Use of RNA interference to inhibit integrin (alpha6beta4)-mediated invasion and migration of breast carcinoma cells. Clinical & Experimental Metastasis, 20, 569–576.Google Scholar
  25. 25.
    Yoon, S. O., Shin, S., & Mercurio, A. M. (2006). Ras stimulation of E2F activity and a consequent E2F regulation of integrin alpha6beta4 promote the invasion of breast carcinoma cells. Cancer Research, 66, 6288–6295.PubMedGoogle Scholar
  26. 26.
    Guo, W., Pylayeva, Y., Pepe, A., Yoshioka, T., Muller, W. J., Inghirami, G., et al. (2006). Beta 4 integrin amplifies ErbB2 signaling to promote mammary tumorigenesis. Cell, 126, 489–502.PubMedGoogle Scholar
  27. 27.
    Gilcrease, M. Z., Zhou, X., Lu, X., Woodward, W. A., Hall, B. E., & Morrissey, P. J. (2009). Alpha6beta4 integrin crosslinking induces EGFR clustering and promotes EGF-mediated Rho activation in breast cancer. Journal of Experimental & Clinical Cancer Research, 28, 67.Google Scholar
  28. 28.
    Vizirianakis, I. S., Yao, C. C., Chen, Y., Ziober, B. L., Tsiftsoglou, A. S., & Kramer, R. H. (2001). Transfection of MCF-7 carcinoma cells with human integrin alpha7 cDNA promotes adhesion to laminin. Archives of Biochemistry and Biophysics, 385, 108–116.PubMedGoogle Scholar
  29. 29.
    Staniszewska, I., Walsh, E. M., Rothman, V. L., Gaathon, A., Tuszynski, G. P., Calvete, J. J., et al. (2009). Effect of VP12 and viperistatin on inhibition of collagen receptors-dependent melanoma metastasis. Cancer Biology & Therapy, 8, 1507–1516.Google Scholar
  30. 30.
    Garamszegi, N., Garamszegi, S. P., Shehadeh, L. A., & Scully, S. P. (2009). Extracellular matrix-induced gene expression in human breast cancer cells. Molecular Cancer Res, 7, 319–329.Google Scholar
  31. 31.
    Van Slambrouck, S., Grijelmo, C., De Wever, O., Bruyneel, E., Emami, S., Gespach, C., et al. (2007). Activation of the FAK-src molecular scaffolds and p130Cas-JNK signaling cascades by alpha1-integrins during colon cancer cell invasion. International Journal of Oncology, 31, 1501–1508.PubMedGoogle Scholar
  32. 32.
    Wang, Y., Wang, X., Zhang, Y., Yang, S., Wang, J., Zhang, X., et al. (2009). RGD-modified polymeric micelles as potential carriers for targeted delivery to integrin-overexpressing tumor vasculature and tumor cells. Journal of Drug Targeting, 17, 459–467.PubMedGoogle Scholar
  33. 33.
    Meyer, T., Marshall, J. F., & Hart, I. R. (1998). Expression of alphav integrins and vitronectin receptor identity in breast cancer cells. British Journal of Cancer, 77, 530–536.PubMedGoogle Scholar
  34. 34.
    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
  35. 35.
    Nieswandt, B., Hafner, M., Echtenacher, B., & Mannel, D. N. (1999). Lysis of tumor cells by natural killer cells in mice is impeded by platelets. Cancer Research, 59, 1295–1300.PubMedGoogle Scholar
  36. 36.
    Huang, J., Roth, R., Heuser, J. E., & Sadler, J. E. (2009). Integrin alpha(v)beta(3) on human endothelial cells binds von Willebrand factor strings under fluid shear stress. Blood, 113, 1589–1597.PubMedGoogle Scholar
  37. 37.
    Putnam, A. J., Schulz, V. V., Freiter, E. M., Bill, H. M., & Miranti, C. K. (2009). Src, PKCalpha, and PKCdelta are required for alphavbeta3 integrin-mediated metastatic melanoma invasion. Cell Commun Signal, 7, 10.PubMedGoogle Scholar
  38. 38.
    Jia, Y., Zeng, Z. Z., Markwart, S. M., Rockwood, K. F., Ignatoski, K. M., Ethier, S. P., et al. (2004). Integrin fibronectin receptors in matrix metalloproteinase-1-dependent invasion by breast cancer and mammary epithelial cells. Cancer Research, 64, 8674–8681.PubMedGoogle Scholar
  39. 39.
    Liu, Y., Pixley, R., Fusaro, M., Godoy, G., Kim, E., Bromberg, M. E., et al. (2009). Cleaved high-molecular-weight kininogen and its domain 5 inhibit migration and invasion of human prostate cancer cells through the epidermal growth factor receptor pathway. Oncogene, 28, 2756–2765.PubMedGoogle Scholar
  40. 40.
    Hall, E. H., Daugherty, A. E., Choi, C. K., Horwitz, A. F., & Brautigan, D. L. (2009). Tensin1 requires protein phosphatase-1alpha in addition to RhoGAP DLC-1 to control cell polarization, migration, and invasion. Journal of Biological Chemistry, 284, 34713–34722.PubMedGoogle Scholar
  41. 41.
    Stanchi, F., Grashoff, C., Nguemeni Yonga, C. F., Grall, D., Fassler, R., & Van Obberghen-Schilling, E. (2009). Molecular dissection of the ILK-PINCH-parvin triad reveals a fundamental role for the ILK kinase domain in the late stages of focal-adhesion maturation. Journal of Cell Science, 122, 1800–1811.PubMedGoogle Scholar
  42. 42.
    Tang, B. L., & Ng, E. L. (2009). Rabs and cancer cell motility. Cell Motility and the Cytoskeleton, 66, 365–370.PubMedGoogle Scholar
  43. 43.
    Giancotti, F. G., & Ruoslahti, E. (1990). Elevated levels of the alpha 5 beta 1 fibronectin receptor suppress the transformed phenotype of Chinese hamster ovary cells. Cell, 60, 849–859.PubMedGoogle Scholar
  44. 44.
    Varner, J. A., Emerson, D. A., & Juliano, R. L. (1995). Integrin alpha 5 beta 1 expression negatively regulates cell growth: reversal by attachment to fibronectin. Molecular Biology of the Cell, 6, 725–740.PubMedGoogle Scholar
  45. 45.
    Imanishi, Y., Hu, B., Jarzynka, M. J., Guo, P., Elishaev, E., Bar-Joseph, I., et al. (2007). Angiopoietin-2 stimulates breast cancer metastasis through the alpha(5)beta(1) integrin-mediated pathway. Cancer Research, 67, 4254–4263.PubMedGoogle Scholar
  46. 46.
    Morozevich, G. E., Kozlova, N. I., Cheglakov, I. B., Ushakova, N. A., Preobrazhenskaya, M. E., & Berman, A. E. (2008). Implication of alpha5beta1 integrin in invasion of drug-resistant MCF-7/ADR breast carcinoma cells: a role for MMP-2 collagenase. Biochemistry (Moscow), 73, 791–796.Google Scholar
  47. 47.
    Zhao, R., Liu, X. Q., Wu, X. P., Liu, Y. F., Zhang, Z. Y., Yang, G. Y., et al. (2009). Vascular endothelial growth factor (VEGF) enhances gastric carcinoma invasiveness via integrin alpha(v)beta6. Cancer Letters, 287(2), 150–156.Google Scholar
  48. 48.
    Shen, S., Fan, J., Cai, B., Lv, Y., Zeng, M., Hao, Y., et al. (2009). Vascular endothelial growth factor enhances cancer cell adhesion to microvascular endothelium in vivo. Experimental Physiology. doi:10.1113/expphysiol.2009.050260.
  49. 49.
    Hausner, S. H., Abbey, C. K., Bold, R. J., Gagnon, M. K., Marik, J., Marshall, J. F., et al. (2009). Targeted in vivo imaging of integrin alphavbeta6 with an improved radiotracer and its relevance in a pancreatic tumor model. Cancer Research, 69, 5843–5850.PubMedGoogle Scholar
  50. 50.
    Defilles, C., Lissitzky, J. C., Montero, M. P., Andre, F., Prevot, C., Delamarre, E., et al. (2009). Alphavbeta5/beta6 integrin suppression leads to a stimulation of alpha2beta1 dependent cell migration resistant to PI3K/Akt inhibition. Experimental Cell Research, 315, 1840–1849.PubMedGoogle Scholar
  51. 51.
    Sawhney, R. S., Liu, W., & Brattain, M. G. (2009). A novel role of ERK5 in integrin-mediated cell adhesion and motility in cancer cells via Fak signaling. Journal of Cellular Physiology, 219, 152–161.PubMedGoogle Scholar
  52. 52.
    Zhao-Yang, Z., Ke-Sen, X., Qing-Si, H., Wei-Bo, N., Jia-Yong, W., Yue-Tang, M., et al. (2008). Signaling and regulatory mechanisms of integrin alphavbeta6 on the apoptosis of colon cancer cells. Cancer Letters, 266, 209–215.PubMedGoogle Scholar
  53. 53.
    Yang, G. Y., Xu, K. S., Pan, Z. Q., Zhang, Z. Y., Mi, Y. T., Wang, J. S., et al. (2008). Integrin alpha v beta 6 mediates the potential for colon cancer cells to colonize in and metastasize to the liver. Cancer Sci, 99, 879–887.PubMedGoogle Scholar
  54. 54.
    Gupta, S. K., & Vlahakis, N. E. (2009). Integrin alpha9beta1 mediates enhanced cell migration through nitric oxide synthase activity regulated by Src tyrosine kinase. Journal of Cell Science, 122, 2043–2054.PubMedGoogle Scholar
  55. 55.
    Jakubowska, A., Rozkrut, D., Antoniou, A., Hamann, U., & Lubinski, J. (2009). The Leu33Pro polymorphism in the ITGB3 gene does not modify BRCA1/2-associated breast or ovarian cancer risks: results from a multicenter study among 15,542 BRCA1 and BRCA2 mutation carriers. Breast Cancer Research and Treatment. doi:10.1007/s10549-009-0595-7.
  56. 56.
    Collier, I. E., Wilhelm, S. M., Eisen, A. Z., Marmer, B. L., Grant, G. A., Seltzer, J. L., et al. (1988). H-ras oncogene-transformed human bronchial epithelial cells (TBE-1) secrete a single metalloprotease capable of degrading basement membrane collagen. Journal of Biological Chemistry, 263, 6579–6587.PubMedGoogle Scholar
  57. 57.
    Monteagudo, C., Merino, M. J., San-Juan, J., Liotta, L. A., & Stetler-Stevenson, W. G. (1990). Immunohistochemical distribution of type IV collagenase in normal, benign, and malignant breast tissue. American Journal of Pathology, 136, 585–592.PubMedGoogle Scholar
  58. 58.
    Liu, A. J., Hu, Y. X., Liu, C. J., Yao, X. L., & Zhang, G. R. (2009). The mechanism of inhibition of metastasis by cartilage polysaccharide in breast-cancer cells. Biotechnology and Applied Biochemistry, 53, 253–263.PubMedGoogle Scholar
  59. 59.
    Grassinger, J., Haylock, D. N., Storan, M. J., Haines, G. O., Williams, B., Whitty, G. A., et al. (2009). Thrombin-cleaved osteopontin regulates hemopoietic stem and progenitor cell functions through interactions with alpha9beta1 and alpha4beta1 integrins. Blood, 114, 49–59.PubMedGoogle Scholar
  60. 60.
    Mi, Z., Guo, H., Russell, M. B., Liu, Y., Sullenger, B. A., & Kuo, P. C. (2009). RNA aptamer blockade of osteopontin inhibits growth and metastasis of MDA-MB231 breast cancer cells. Molecular Ther, 17, 153–161.Google Scholar
  61. 61.
    Behera, R., Kumar, V., Lohite, K., Karnik, S., & Kundu, G. C. (2009). Activation of JAK2/STAT3 signaling by osteopontin promotes tumor growth in human breast cancer cells. Carcinogenesis (in press).Google Scholar
  62. 62.
    El-Tanani, M. K., Jin, D., Campbell, F. C., & Johnston, P. G. (2009). Interferon-induced transmembrane 3 binds osteopontin in vitro: expressed in vivo IFITM3 reduced OPN expression. Oncogene. doi:10.1038/onc.2009.379.
  63. 63.
    Conway, C., Mitra, A., Jewell, R., Randerson-Moor, J., Lobo, S., Nsengimana, J., et al. (2009). Gene expression profiling of paraffin-embedded primary melanoma using the DASL assay identifies increased osteopontin expression as predictive of reduced relapse-free survival. Clinical Cancer Research, 15, 6939–6946.PubMedGoogle Scholar
  64. 64.
    Robertson, B. W., & Chellaiah, M. A. (2010). Osteopontin induces beta-catenin signaling through activation of Akt in prostate cancer cells. Experimental Cell Research, 316, 1–11.PubMedGoogle Scholar
  65. 65.
    Beauvais, D. M., Ell, B. J., McWhorter, A. R., & Rapraeger, A. C. (2009). Syndecan-1 regulates alphavbeta3 and alphavbeta5 integrin activation during angiogenesis and is blocked by synstatin, a novel peptide inhibitor. Journal of Experimental Medicine, 206, 691–705.PubMedGoogle Scholar
  66. 66.
    Shao, R., Hamel, K., Petersen, L., Cao, Q. J., Arenas, R. B., Bigelow, C., et al. (2009). YKL-40, a secreted glycoprotein, promotes tumor angiogenesis. Oncogene (in press).Google Scholar
  67. 67.
    Dome, B., Raso, E., Dobos, J., Meszaros, L., Varga, N., Puskas, L. G., et al. (2005). Parallel expression of alphaIIbbeta3 and alphavbeta3 integrins in human melanoma cells upregulates bFGF expression and promotes their angiogenic phenotype. International Journal of Cancer, 116, 27–35.Google Scholar
  68. 68.
    Ohtoshi, A., Maeda, T., Higashi, H., Ashizawa, S., Yamada, M., & Hatakeyama, M. (2000). Beta3-endonexin as a novel inhibitor of cyclin A-associated kinase. Biochemical and Biophysical Research Communications, 267, 947–952.PubMedGoogle Scholar
  69. 69.
    Wang, M. Y., Chen, P. S., Prakash, E., Hsu, H. C., Huang, H. Y., Lin, M. T., et al. (2009). Connective tissue growth factor confers drug resistance in breast cancer through concomitant up-regulation of Bcl-xL and cIAP1. Cancer Research, 69, 3482–3491.PubMedGoogle Scholar
  70. 70.
    Hui, L., Ji, C., Hui, B., Lv, T., Ha, X., Yang, J., et al. (2009). The oncoprotein LMO3 interacts with calcium- and integrin-binding protein CIB. Brain Research, 1265, 24–29.PubMedGoogle Scholar
  71. 71.
    Denofrio, J. C., Yuan, W., Temple, B. R., Gentry, H. R., & Parise, L. V. (2008). Characterization of calcium- and integrin-binding protein 1 (CIB1) knockout platelets: potential compensation by CIB family members. Thrombosis and Haemostasis, 100, 847–856.PubMedGoogle Scholar
  72. 72.
    Naik, M. U., & Naik, U. P. (2003). Calcium-and integrin-binding protein regulates focal adhesion kinase activity during platelet spreading on immobilized fibrinogen. Blood, 102, 3629–3636.PubMedGoogle Scholar
  73. 73.
    Haataja, L., Kaartinen, V., Groffen, J., & Heisterkamp, N. (2002). The small GTPase Rac3 interacts with the integrin-binding protein CIB and promotes integrin alpha(IIb)beta(3)-mediated adhesion and spreading. Journal of Biological Chemistry, 277, 8321–8328.PubMedGoogle Scholar
  74. 74.
    Mardilovich, K., & Shaw, L. M. (2009). Hypoxia regulates insulin receptor substrate-2 expression to promote breast carcinoma cell survival and invasion. Cancer Research, 69, 8894–8901.PubMedGoogle Scholar
  75. 75.
    Yang, S. N., Chen, H. T., Tsou, H. K., Huang, C. Y., Yang, W. H., Su, C. M., et al. (2009). Leptin enhances cell migration in human chondrosarcoma cells through OBRl leptin receptor. Carcinogenesis, 30, 566–574.PubMedGoogle Scholar
  76. 76.
    Geiger, C., Nagel, W., Boehm, T., van Kooyk, Y., Figdor, C. G., Kremmer, E., et al. (2000). Cytohesin-1 regulates beta-2 integrin-mediated adhesion through both ARF-GEF function and interaction with LFA-1. EMBO Journal, 19, 2525–2536.PubMedGoogle Scholar
  77. 77.
    D'Alessio, S., & Blasi, F. (2009). The urokinase receptor as an entertainer of signal transduction. Frontiers in Bioscience, 14, 4575–4587.PubMedGoogle Scholar
  78. 78.
    Sawai, H., Okada, Y., Funahashi, H., Matsuo, Y., Takahashi, H., Takeyama, H., et al. (2006). Interleukin-1alpha enhances the aggressive behavior of pancreatic cancer cells by regulating the alpha6beta1-integrin and urokinase plasminogen activator receptor expression. BMC Cell Biol, 7, 8.PubMedGoogle Scholar
  79. 79.
    Aguirre Ghiso, J. A., Kovalski, K., & Ossowski, L. (1999). Tumor dormancy induced by downregulation of urokinase receptor in human carcinoma involves integrin and MAPK signaling. Journal of Cell Biology, 147, 89–104.PubMedGoogle Scholar
  80. 80.
    Degani, S., Balzac, F., Brancaccio, M., Guazzone, S., Retta, S. F., Silengo, L., et al. (2002). The integrin cytoplasmic domain-associated protein ICAP-1 binds and regulates Rho family GTPases during cell spreading. Journal of Cell Biology, 156, 377–387.PubMedGoogle Scholar
  81. 81.
    Stroeken, P. J., Alvarez, B., Van Rheenen, J., Wijnands, Y. M., Geerts, D., Jalink, K., et al. (2006). Integrin cytoplasmic domain-associated protein-1 (ICAP-1) interacts with the ROCK-I kinase at the plasma membrane. Journal of Cellular Physiology, 208, 620–628.PubMedGoogle Scholar
  82. 82.
    Fournier, H. N., Dupe-Manet, S., Bouvard, D., Luton, F., Degani, S., Block, M. R., et al. (2005). Nuclear translocation of integrin cytoplasmic domain-associated protein 1 stimulates cellular proliferation. Molecular Biology of the Cell, 16, 1859–1871.PubMedGoogle Scholar
  83. 83.
    Millon-Fremillon, A., Bouvard, D., Grichine, A., Manet-Dupe, S., Block, M. R., & Albiges-Rizo, C. (2008). Cell adaptive response to extracellular matrix density is controlled by ICAP-1-dependent beta1-integrin affinity. Journal of Cell Biology, 180, 427–441.PubMedGoogle Scholar
  84. 84.
    Bouvard, D., Aszodi, A., Kostka, G., Block, M. R., Albiges-Rizo, C., & Fassler, R. (2007). Defective osteoblast function in ICAP-1-deficient mice. Development, 134, 2615–2625.PubMedGoogle Scholar
  85. 85.
    D'Amico, M., Hulit, J., Amanatullah, D. F., Zafonte, B. T., Albanese, C., Bouzahzah, B., et al. (2000). The integrin-linked kinase regulates the cyclin D1 gene through glycogen synthase kinase 3beta and cAMP-responsive element-binding protein-dependent pathways. Journal of Biological Chemistry, 275, 32649–32657.PubMedGoogle Scholar
  86. 86.
    Vasala, K., Kuvaja, P., & Turpeenniemi-Hujanen, T. (2008). Low circulating levels of ProMMP-2 are associated with adverse prognosis in bladder cancer. Tumour Biology, 29, 279–286.PubMedGoogle Scholar
  87. 87.
    Staack, A., Badendieck, S., Schnorr, D., Loening, S. A., & Jung, K. (2006). Combined determination of plasma MMP2, MMP9, and TIMP1 improves the non-invasive detection of transitional cell carcinoma of the bladder. BMC Urol, 6, 19.PubMedGoogle Scholar
  88. 88.
    Fan, Y. Z., Zhao, Z. M., Fu, J. Y., & Chen, C. Q. (2006). Anti-tumor mechanism of norcantharidin for the implanted tumors of human gallbladder carcinoma in nude mice in vivo. Zhonghua WaiKe ZaZhi, 44, 618–622.PubMedGoogle Scholar
  89. 89.
    Hyder, S. M., Liang, Y., & Wu, J. (2009). Estrogen regulation of thrombospondin-1 in human breast cancer cells. International Journal of Cancer, 125, 1045–1053.Google Scholar
  90. 90.
    Lindberg, K., Strom, A., Lock, J. G., Gustafsson, J. A., Haldosen, L. A., & Helguero, L. A. (2010). Expression of estrogen receptor beta increases integrin alpha1 and integrin beta1 levels and enhances adhesion of breast cancer cells. Journal of Cellular Physiology, 222, 156–167.PubMedGoogle Scholar
  91. 91.
    Terraube, V., Marx, I., & Denis, C. V. (2007). Role of von Willebrand factor in tumor metastasis. Thrombosis Research, 120(Suppl 2), S64–S70.PubMedGoogle Scholar
  92. 92.
    Terraube, V., Pendu, R., Baruch, D., Gebbink, M. F., Meyer, D., Lenting, P. J., et al. (2006). Increased metastatic potential of tumor cells in von Willebrand factor-deficient mice. Journal of Thrombosis Haemost, 4, 519–526.Google Scholar
  93. 93.
    Gomes, N., Legrand, C., & Fauvel-Lafeve, F. (2005). Shear stress induced release of von Willebrand factor and thrombospondin-1 in HUVEC extracellular matrix enhances breast tumour cell adhesion. Clinical & Experimental Metastasis, 22, 215–223.Google Scholar
  94. 94.
    Gil-Bazo, I., Catalan, V., Paramo, J., Quero, C., Escriva de Romani, S., Perez-Ochoa, A., et al. (2003). Von Willebrand factor as an intermediate between hemostasis and angiogenesis of tumor origin. Revista de Medicina de la Universidad de Navarra, 47, 22–28.PubMedGoogle Scholar
  95. 95.
    Jockusch, B. M., Bubeck, P., Giehl, K., Kroemker, M., Moschner, J., Rothkegel, M., et al. (1995). The molecular architecture of focal adhesions. Annual Review of Cell and Developmental Biology, 11, 379–416.PubMedGoogle Scholar
  96. 96.
    Burridge, K., & Chrzanowska-Wodnicka, M. (1996). Focal adhesions, contractility, and signaling. Annual Review of Cell and Developmental Biology, 12, 463–518.PubMedGoogle Scholar
  97. 97.
    Lo, S. H., Weisberg, E., & Chen, L. B. (1994). Tensin: a potential link between the cytoskeleton and signal transduction. Bioessays, 16, 817–823.PubMedGoogle Scholar
  98. 98.
    Alahari, S. K., Lee, J. W., & Juliano, R. L. (2000). Nischarin, a novel protein that interacts with the integrin alpha5 subunit and inhibits cell migration. Journal of Cell Biology, 151, 1141–1154.PubMedGoogle Scholar
  99. 99.
    Ding, Y., Milosavljevic, T., & Alahari, S. K. (2008). Nischarin inhibits LIM kinase to regulate cofilin phosphorylation and cell invasion. Molecular and Cellular Biology, 28, 3742–3756.PubMedGoogle Scholar
  100. 100.
    Juliano, R. L., Reddig, P., Alahari, S., Edin, M., Howe, A., & Aplin, A. (2004). Integrin regulation of cell signalling and motility. Biochemical Society Transactions, 32, 443–446.PubMedGoogle Scholar
  101. 101.
    Chia, W. J., & Tang, B. L. (2009). Emerging roles for Rab family GTPases in human cancer. Biochimica et Biophysica Acta, 1795, 110–116.PubMedGoogle Scholar
  102. 102.
    Bridger, P. S., Haupt, S., Leiser, R., Johnson, G. A., Burghardt, R. C., Tinneberg, H. R., et al. (2008). Integrin activation in bovine placentomes and in caruncular epithelial cells isolated from pregnant cows. Biology of Reproduction, 79, 274–282.PubMedGoogle Scholar
  103. 103.
    Critchley, D. R. (2009). Biochemical and structural properties of the integrin-associated cytoskeletal protein talin. Annual Review of Biophysics, 38, 235–254.PubMedGoogle Scholar
  104. 104.
    Wang, J., Wan, W., Sun, R., Liu, Y., Sun, X., Ma, D., et al. (2008). Reduction of Akt2 expression inhibits chemotaxis signal transduction in human breast cancer cells. Cellular Signalling, 20, 1025–1034.PubMedGoogle Scholar
  105. 105.
    van Rheenen, J., Song, X., van Roosmalen, W., Cammer, M., Chen, X., Desmarais, V., et al. (2007). EGF-induced PIP2 hydrolysis releases and activates cofilin locally in carcinoma cells. Journal of Cell Biology, 179, 1247–1259.PubMedGoogle Scholar
  106. 106.
    Payne, S. L., Hendrix, M. J., & Kirschmann, D. A. (2006). Lysyl oxidase regulates actin filament formation through the p130(Cas)/Crk/DOCK180 signaling complex. Journal of Cellular Biochemistry, 98, 827–837.PubMedGoogle Scholar
  107. 107.
    Yamaguchi, H., Lorenz, M., Kempiak, S., Sarmiento, C., Coniglio, S., Symons, M., et al. (2005). Molecular mechanisms of invadopodium formation: the role of the N-WASP-Arp2/3 complex pathway and cofilin. Journal of Cell Biology, 168, 441–452.PubMedGoogle Scholar
  108. 108.
    Uruno, T., Liu, J., Zhang, P., Fan, Y., Egile, C., Li, R., et al. (2001). Activation of Arp2/3 complex-mediated actin polymerization by cortactin. Nature Cell Biology, 3, 259–266.PubMedGoogle Scholar
  109. 109.
    Lorenz, M., Yamaguchi, H., Wang, Y., Singer, R. H., & Condeelis, J. (2004). Imaging sites of N-wasp activity in lamellipodia and invadopodia of carcinoma cells. Current Biology, 14, 697–703.PubMedGoogle Scholar
  110. 110.
    Katz, M., Amit, I., Citri, A., Shay, T., Carvalho, S., Lavi, S., et al. (2007). A reciprocal tensin-3-cten switch mediates EGF-driven mammary cell migration. Nature Cell Biology, 9, 961–969.PubMedGoogle Scholar
  111. 111.
    Friedland, J. C., Lee, M. H., & Boettiger, D. (2009). Mechanically activated integrin switch controls alpha5beta1 function. Science, 323, 642–644.PubMedGoogle Scholar
  112. 112.
    Lee, J. H., Rangarajan, E. S., Yogesha, S. D., & Izard, T. (2009). Raver1 interactions with vinculin and RNA suggest a feed-forward pathway in directing mRNA to focal adhesions. Structure, 17, 833–842.PubMedGoogle Scholar
  113. 113.
    Zhang, B., Gu, F., She, C., Guo, H., Li, W., Niu, R., et al. (2009). Reduction of Akt2 inhibits migration and invasion of glioma cells. International Journal of Cancer, 125, 585–595.Google Scholar
  114. 114.
    Reynolds, A. R., Hart, I. R., Watson, A. R., Welti, J. C., Silva, R. G., Robinson, S. D., et al. (2009). Stimulation of tumor growth and angiogenesis by low concentrations of RGD-mimetic integrin inhibitors. Nature Medicine, 15, 392–400.PubMedGoogle Scholar
  115. 115.
    Barkan, D., Kleinman, H., Simmons, J. L., Asmussen, H., Kamaraju, A. K., Hoenorhoff, M. J., et al. (2008). Inhibition of metastatic outgrowth from single dormant tumor cells by targeting the cytoskeleton. Cancer Research, 68, 6241–6250.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular Biology, Stanley S. Scott Cancer CenterLSU School of MedicineNew OrleansUSA

Personalised recommendations