Skip to main content

Advertisement

SpringerLink
Log in

Signal cross talks for sustained MAPK activation and cell migration: the potential role of reactive oxygen species

  • NON-THEMATIC REVIEW
  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

Signal transduction exerted by the microenvironment around the primary tumor locus may trigger tumor metastasis especially at the migration stage. Sustained mitogen activated protein kinase (MAPK) signaling involved in uncontrolled tumor cell migration rely on the cross talks between integrin, receptor tyrosine kinase (RTK) and protein kinase C (PKC). The molecular mechanisms for cross talking between these migration-related signal cascades leading to sustained cell migration are reviewed, focusing on the focal adhesion scaffold protein paxillin as the platform for signal integration. We proposed reactive oxygen species (ROS) as the critical signal messenger sustaining these signal cascades. For the cross talk of integrin with RTK, ROS may suppress paxillin-associated protein tyrosine phosphatase (PTP–PEST) relieving its negative regulatory effects. For the cross talk of integrin with PKC, PKC itself may phosphorylate integrin or paxillin-associated focal adhesion proteins to induce generation of ROS which may reactivate PKC. In the future, ROS will be validated as the promising therapeutic targets for prevention of tumor metastasis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Christofori, G. (2006). New signals from the invasive front (review). Nature, 441(7092), 444–450.

    Article  PubMed  CAS  Google Scholar 

  2. Cairns, R. A., Khokha, R., & Hill, R. P. (2003). Molecular mechanisms of tumor invasion and metastasis: An integrated view. Current Molecular Medicine, 3(7), 659–671.

    Article  PubMed  CAS  Google Scholar 

  3. Sung, S. Y., Hsieh, C. L., Wu, D., Chung, L. W., & Johnstone, P. A. (2007). Tumor microenvironment promotes cancer progression, metastasis, and therapeutic resistance. Current Problems in Cancer, 31(2), 36–100.

    Article  PubMed  Google Scholar 

  4. Ridley, A. J., Schwartz, M. A., Burridge, K., Firtel, R. A., Ginsberg, M. H., Borisy, G., et al. (2003). Cell migration: Integrating signals from front to back. Science, 302(5651), 1704–1709.

    Article  PubMed  CAS  Google Scholar 

  5. Gao, C. F., & Vande Woude, G. F. (2005). HGF/SF-Met signaling in tumor progression. Cell Research, 15(1), 49–51.

    Article  PubMed  Google Scholar 

  6. Bierie, B., & Moses, H. L. (2006). Tumour microenvironment: TGFbeta: The molecular Jekyll and Hyde of cancer. Nature Reviews Cancer, 6(7), 506–520.

    Article  PubMed  CAS  Google Scholar 

  7. Kim, H., & Muller, W. J. (1999). The role of the epidermal growth factor receptor family in mammary tumorigenesis and metastasis. Experimental Cell Research, 253(1), 78–87.

    Article  PubMed  CAS  Google Scholar 

  8. Qiang, Y. W., Walsh, K., Yao, L., Kedei, N., Blumberg, P. M., Rubin, J. S., et al. (2005). Wnts induce migration and invasion of myeloma plasma cells. Blood, 106(5), 1786–1793.

    Article  PubMed  CAS  Google Scholar 

  9. Johnson, G. L., & Lapadat, R. (2002). Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science, 298(5600), 1911–1912.

    Article  PubMed  CAS  Google Scholar 

  10. Huang, C., Jacobson, K., & Schaller, M. D. (2004). MAP kinases and cell migration. Journal of Cell Science, 117(Pt 20), 4619–4628.

    Article  PubMed  CAS  Google Scholar 

  11. Galabova-Kovacs, G., Kolbus, A., Matzen, D., Meissl, K., Piazzolla, D., Rubiolo, C., et al. (2006). ERK and beyond: insights from B-Raf and Raf-1 conditional knockouts. Cell Cycle, 5(14), 1514–1518.

    PubMed  CAS  Google Scholar 

  12. von Kriegsheim, A., Pitt, A., Grindlay, G. J., Kolch, W., & Dhillon, A. S. (2006). Regulation of the Raf–MEK–ERK pathway by protein phosphatase 5. Nature Cell Biology, 8(9), 1011–1016.

    Article  CAS  Google Scholar 

  13. Rajalingam, K., Wunder, C., Brinkmann, V., Churin, Y., Hekman, M., Sievers, C., et al. (2005). Prohibitin is required for Ras-induced Raf–MEK–ERK activation and epithelial cell migration. Nature Cell Biology, 7(8), 837–843.

    Article  PubMed  CAS  Google Scholar 

  14. Giehl, K. (2005). Oncogenic Ras in tumour progression and metastasis. Biological Chemistry, 386(3), 193–205.

    Article  PubMed  CAS  Google Scholar 

  15. Shin, I., Kim, S., Song, H., Kim, H. R., & Moon, A. (2005). H-Ras-specific activation of Rac-MKK3/6-p38 pathway: its critical role in invasion and migration of breast epithelial cells. Journal of Biological Chemistry, 280(15), 14675–14683.

    Article  PubMed  CAS  Google Scholar 

  16. Veit, C., Genze, F., Menke, A., Hoeffert, S., Gress, T. M., Gierschik, P., et al. (2004). Activation of phosphatidylinositol 3-kinase and extracellular signal-regulated kinase is required for glial cell line-derived neurotrophic factor-induced migration and invasion of pancreatic carcinoma cells. Cancer Research, 64(15), 5291–5300.

    Article  PubMed  CAS  Google Scholar 

  17. Woods, D., Cherwinski, H., Venetsanakos, E., Bhat, A., Gysin, S., Humbert, M., et al. (2001). Induction of beta3-integrin gene expression by sustained activation of the Ras-regulated Raf-MEK-extracellular signal-regulated kinase signaling pathway. Molecular and Cellular Biology, 21(9), 3192–3205.

    Article  PubMed  CAS  Google Scholar 

  18. Imamichi, Y., & Menke, A. (2007). Signaling pathways involved in collagen-induced disruption of the E-cadherin complex during epithelial–mesenchymal transition. Cells Tissues Organs, 185(1–3), 180–190.

    Article  PubMed  CAS  Google Scholar 

  19. Yan, F., Hui, Y. N., Li, Y. J., Guo, C. M., & Meng, H. (2007). Epidermal growth factor receptor in cultured human retinal pigment epithelial cells. Ophthalmologica, 221(4), 244–250.

    Article  PubMed  CAS  Google Scholar 

  20. Matsumoto, T., Yokote, K., Tamura, K., Takemoto, M., Ueno, H., Saito, Y., et al. (1999). Platelet-derived growth factor activates p38 mitogen-activated protein kinase through a Ras-dependent pathway that is important for actin reorganization and cell migration. Journal of Biological Chemistry, 274(20), 13954–13960.

    Article  PubMed  CAS  Google Scholar 

  21. Guo, W., & Giancotti, F. G. (2004). Integrin signalling during tumour progression. Nature Reviews. Molecular cell biology, 5(10), 816–826.

    Article  PubMed  CAS  Google Scholar 

  22. Kurayoshi, M., Oue, N., Yamamoto, H., Kishida, M., Inoue, A., Asahara, T., et al. (2006). Expression of Wnt-5a is correlated with aggressiveness of gastric cancer by stimulating cell migration and invasion. Cancer Research, 66(21), 10439–10448.

    Article  PubMed  CAS  Google Scholar 

  23. Abassi, Y. A., & Vuori, K. (2002). Tyrosine 221 in Crk regulates adhesion-dependent membrane localization of Crk and Rac and activation of Rac signaling. EMBO Journal, 21(17), 4571–4582.

    Article  PubMed  CAS  Google Scholar 

  24. Hsia, D. A., Mitra, S. K., Hauck, C. R., Streblow, D. N., Nelson, J. A., Ilic, D., et al. (2003). Differential regulation of cell motility and invasion by FAK. Journal of Cell Biology, 160(5), 753–767.

    Article  PubMed  CAS  Google Scholar 

  25. Rucci, N., DiGiacinto, C., Orru, L., Millimaggi, D., Baron, R., & Teti, A. (2005). A novel protein kinase C alpha-dependent signal to ERK1/2 activated by alphaVbeta3 integrin in osteoclasts and in Chinese hamster ovary (CHO) cells. Journal of Cell Science, 118(Pt 15), 3263–3275.

    Article  PubMed  CAS  Google Scholar 

  26. Desban, N., Lissitzky, J. C., Rousselle, P., & Duband, J. L. (2006). alpha1beta1-integrin engagement to distinct laminin-1 domains orchestrates spreading, migration and survival of neural crest cells through independent signaling pathways. Journal of Cell Science, 119(Pt 15), 3206–3218.

    Article  PubMed  CAS  Google Scholar 

  27. Kermorgant, S., Zicha, D., & Parker, P. J. (2004). PKC controls HGF-dependent c-Met traffic, signalling and cell migration. EMBO Journal, 23(19), 3721–3734.

    Article  PubMed  CAS  Google Scholar 

  28. Tian, Y. C., Chen, Y. C., Chang, C. T., Hung, C. C., Wu, M. S., Phillips, A., et al. (2007). Epidermal growth factor and transforming growth factor-beta1 enhance HK-2 cell migration through a synergistic increase of matrix metalloproteinase and sustained activation of ERK signaling pathway. Experimental Cell Research, 313(11), 2367–2377.

    Article  PubMed  CAS  Google Scholar 

  29. Mercer, K., Giblett, S., Oakden, A., Brown, J., Marais, R., & Pritchard, C. (2005). A-Raf and Raf-1 work together to influence transient ERK phosphorylation and Gl/S cell cycle progression. Oncogene, 24(33), 5207–5217.

    Article  PubMed  CAS  Google Scholar 

  30. Kim, S. J., Kim, S. Y., Kwon, C. H., & Kim, Y. K. (2007). Differential effect of FGF and PDGF on cell proliferation and migration in osteoblastic cells. Growth Factors, 25(2), 77–86.

    Article  PubMed  CAS  Google Scholar 

  31. McCawley, L. J., Li, S., Wattenberg, E. V., & Hudson, L. G. (1999). Sustained activation of the mitogen-activated protein kinase pathway. A mechanism underlying receptor tyrosine kinase specificity for matrix metalloproteinase-9 induction and cell migration. Journal of Biological Chemistry, 274(7), 4347–4353.

    Article  PubMed  CAS  Google Scholar 

  32. Krueger, J. S., Keshamouni, V. G., Atanaskova, N., & Reddy, K. B. (2001). Temporal and quantitative regulation of mitogen-activated protein kinase (MAPK) modulates cell motility and invasion. Oncogene, 20(31), 4209–4218.

    Article  PubMed  CAS  Google Scholar 

  33. lin, E. J., Opresko, L. K., Wells, A., Wiley, H. S., & Lauffenburger, D. A. (2007). EGF-receptor- mediated mammary epithelial cell migration is driven by sustained ERK signaling from autocrine stimulation. Journal of Cell Science, 120(Pt 20), 3688–3699.

    Google Scholar 

  34. Suyama, K., Shapiro, I., Guttman, M., & Hazan, R. B. (2002). A signaling pathway leading to metastasis is controlled by N-cadherin and the FGF receptor. Cancer Cell, 2(4), 301–314.

    Article  PubMed  CAS  Google Scholar 

  35. Pukac, L., Huangpu, J., & Karnovsky, M. J. (1998). Platelet-derived growth factor-BB, insulin-like growth factor-I, and phorbol ester activate different signaling pathways for stimulation of vascular smooth muscle cell migration. Experimental Cell Research, 242(2), 548–560.

    Article  PubMed  CAS  Google Scholar 

  36. Wu, W. S., Tsai, R. K., Chang, C. H., Wang, S., Wu, J. R., & Chang, Y. X. (2006). Reactive oxygen species mediated sustained activation of protein kinase C alpha and extracellular signal-regulated kinase for migration of human hepatoma cell Hepg2. Molecular Cancer Research, 4(10), 747–758.

    Article  PubMed  CAS  Google Scholar 

  37. Levy, Y., Ronen, D., Bershadsky, A. D., & Zick, Y. (2003). Sustained induction of ERK, protein kinase B, and p70 S6 kinase regulates cell spreading and formation of F-actin microspikes upon ligation of integrins by galectin-8, a mammalian lectin. Journal of Biological Chemistry, 278(16), 14533–14542.

    Article  PubMed  CAS  Google Scholar 

  38. Meier, F., Busch, S., Gast, D., Goppert, A., Altevogt, P., Maczey, E., et al. (2006). The adhesion molecule L1 (CD171) promotes melanoma progression. International Journal of Cancer, 119(3), 549–555.

    Article  CAS  Google Scholar 

  39. Woods, D., Cherwinski, H., Venetsanakos, E., Bhat, A., Gysin, S., Humbert, M., et al. (2001). Induction of beta3-integrin gene expression by sustained activation of the Ras-regulated Raf-MEK-extracellular signal-regulated kinase signaling pathway. Molecular and Cellular Biology, 21(9), 3192–3205.

    Article  PubMed  CAS  Google Scholar 

  40. Katz, M., Amit, I., & Yarden, Y. (2007). Regulation of MAPKs by growth factors and receptor tyrosine kinases. Biochimica et Biophysica Acta, 1773(8), 1161–1176.

    PubMed  CAS  Google Scholar 

  41. Silletti, S., Yebra, M., Perez, B., Cirulli, V., McMahon, M., & Montgomery, A. M. (2004). Extracellular signal-regulated kinase (ERK)-dependent gene expression contributes to L1 cell adhesion molecule-dependent motility and invasion. Journal of Biological Chemistry, 279(28), 28880–28888.

    Article  PubMed  CAS  Google Scholar 

  42. Ishibe, S., Joly, D., Liu, Z. X., & Cantley, L. G. (2004). Paxillin serves as an ERK-regulated scaffold for coordinating FAK and Rac activation in epithelial morphogenesis. Molecular Cell, 16(2), 257–267.

    Article  PubMed  CAS  Google Scholar 

  43. Giancotti, F. G., & Ruoslahti, E. (1999). Integrin signaling. Science, 285(5430), 1028–1032.

    Article  PubMed  CAS  Google Scholar 

  44. Mitra, S. K., & Schlaepfer, D. D. (2006). Integrin-regulated FAK-Src signaling in normal and cancer cells. Current Opinion in Cell Biology, 18(5), 516–523.

    Article  PubMed  CAS  Google Scholar 

  45. Hood, J. D., & Cheresh, D. A. (2002). Role of integrins in cell invasion and migration. Nature Reviews. Cancer, 2(2), 91–100.

    Article  PubMed  Google Scholar 

  46. Chiarugi, P., & Fiaschi, T. (2007). Redox signalling in anchorage-dependent cell growth. Cell Signal, 19(4), 672–682.

    Article  PubMed  CAS  Google Scholar 

  47. Friedman, A., & Perrimon, N. (2006). A functional RNAi screen for regulators of receptor tyrosine kinase and ERK signalling. Nature, 444(7116), 230–234.

    Article  PubMed  CAS  Google Scholar 

  48. Giancotti, F. G., & Tarone, G. (2003). Positional control of cell fate through joint integrin/receptor protein kinase signaling. Annual Review of Cell and Developmental Biology, 19, 173–206.

    Article  PubMed  CAS  Google Scholar 

  49. Borges, E., Jan, Y., & Ruoslahti, E. (2000). Platelet-derived growth factor receptor beta and vascular endothelial growth factor receptor 2 bind to the beta 3 integrin through its extracellular domain. Journal of Biological Chemistry, 275(51), 39867–39873.

    Article  PubMed  CAS  Google Scholar 

  50. Short, S. M., Boyer, J. L., & Juliano, R. L. (2000). Integrins regulate the linkage between upstream and downstream events in G protein-coupled receptor signaling to mitogen-activated protein kinase. Journal of Biological Chemistry, 275(17), 12970–12977.

    Article  PubMed  CAS  Google Scholar 

  51. 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(3), 489–502.

    Article  PubMed  CAS  Google Scholar 

  52. Clemmons, D. R., & Maile, L. A. (2005). Interaction between insulin-like growth factor-I receptor and alphaVbeta3 integrin linked signaling pathways: cellular responses to changes in multiple signaling inputs. Molecular Endocrinology, 19(1), 1–11.

    Article  PubMed  CAS  Google Scholar 

  53. Miyamoto, S., Teramoto, H., Gutkind, J. S., & Yamada, K. M. (1996). Integrins can collaborate with growth factors for phosphorylation of receptor tyrosine kinases and MAP kinase activation: roles of integrin aggregation and occupancy of receptors. Journal of Cell Biology, 135(6 Pt 1), 1633–1642.

    Article  PubMed  CAS  Google Scholar 

  54. Turner, C. E. (2000). Paxillin interactions. Journal of Cell Science, 113(Pt 23), 4139–4140.

    PubMed  CAS  Google Scholar 

  55. Gilcrease, M. Z. (2007). Integrin signaling in epithelial cells. Cancer Letters, 247(1), 1–25.

    Article  PubMed  CAS  Google Scholar 

  56. Li, F., Zhang, Y., & Wu, C. (1999). Integrin-linked kinase is localized to cell-matrix focal adhesions but not cell-cell adhesion sites and the focal adhesion localization of integrin-linked kinase is regulated by the PINCH-binding ANK repeats. Journal of Cell Science, 112(Pt 24), 4589–4599.

    PubMed  CAS  Google Scholar 

  57. Tu, Y., Li, F., & Wu, C. (1998). Nck-2, a novel Src homology2/3-containing adaptor protein that interacts with the LIM-only protein PINCH and components of growth factor receptor kinase-signaling pathways. Molecular Biology of the Cell, 9(12), 3367–3382.

    PubMed  CAS  Google Scholar 

  58. ffrench-Constant, C., & Colognato, H. (2004). Integrins: Versatile integrators of extracellular signals. Trends in Cell Biology, 14(12), 678–686.

    Article  PubMed  CAS  Google Scholar 

  59. Chan, P. C., Chen, S. Y., Chen, C. H., & Chen, H. C. (2006). Crosstalk between hepatocyte growth factor and integrin signaling pathways. Journal of Biomedical Science, 13(2), 215–223.

    Article  PubMed  CAS  Google Scholar 

  60. Playford, M. P., & Schaller, M. D. (2004). The interplay between Src and integrins in normal and tumor biology. Oncogene, 23, 7928–7946.

    Article  PubMed  CAS  Google Scholar 

  61. Mitra, S. K., & Schlaepfer, D. D. (2006). Integrin-regulated FAK-Src signaling in normal and cancer cells. Current Opinion in Cell Biology, 18(5), 516–523.

    Article  PubMed  CAS  Google Scholar 

  62. Zaidel-Bar, R., Milo, R., Kam, Z., & Geiger, B. (2007). A paxillin tyrosine phosphorylation switch regulates the assembly and form of cell-matrix adhesions. Journal of Cell Science, 120(Pt 1), 137–148.

    PubMed  CAS  Google Scholar 

  63. Brown, M. C., & Turner, C. E. (2004). Paxillin: adapting to change. Physiological Reviews, 84(4), 1315–1339.

    Article  PubMed  CAS  Google Scholar 

  64. Waters, C. M., Connell, M. C., Pyne, S., & Pyne, N. J. (2005). c-Src is involved in regulating signal transmission from PDGFbeta receptor-GPCR(s) complexes in mammalian cells. Cell Signal, 17(2), 263–277.

    Article  PubMed  CAS  Google Scholar 

  65. Mon, N. N., Ito, S., Senga, T., & Hamaguchi, M. (2006). FAK signaling in neoplastic disorders: a linkage between inflammation and cancer. Annals of the New York Academy of Sciences, 1086, 199–212.

    Article  PubMed  CAS  Google Scholar 

  66. Park, S. Y., Li, H., & Avraham, S. (2007). RAFTK/Pyk2 regulates EGF-induced PC12 cell spreading and movement. Cell Signal, 19(2), 289–300.

    Article  PubMed  CAS  Google Scholar 

  67. Monami, G., Gonzalez, E. M., Hellman, M., Gomella, L. G., Baffa, R., Iozzo, R. V., et al. (2006). Proepithelin promotes migration and invasion of 5637 bladder cancer cells through the activation of ERK1/2 and the formation of a paxillin/FAK/ERK complex. Cancer Research, 66(14), 7103–7110.

    Article  PubMed  CAS  Google Scholar 

  68. Lesslie, D. P., Summy, J. M., Parikh, N. U., Fan, F., Trevino, J. G., Sawyer, T. K., et al. (2006). Vascular endothelial growth factor receptor-1 mediates migration of human colorectal carcinoma cells by activation of Src family kinases. British Journal of Cancer, 94(11), 1710–1717.

    PubMed  CAS  Google Scholar 

  69. Ishibe, S., Joly, D., Zhu, X., & Cantley, L. G. (2003). Phosphorylation-dependent paxillin–ERK association mediates hepatocyte growth factor-stimulated epithelial morphogenesis. Molecular Cell, 12(5), 1275–1285.

    Article  PubMed  CAS  Google Scholar 

  70. Manser, E., Loo, T. H., Koh, C. G., Zhao, Z. S., Chen, X. Q., Tan, L., et al. (1998). PAK kinases are directly coupled to the PIX family of nucleotide exchange factors. Molecular Cell, 1(2), 183–192.

    Article  PubMed  CAS  Google Scholar 

  71. West, K. A., Zhang, H., Brown, M. C., Nikolopoulos, S. N., Riedy, M. C., Horwitz, A. F., et al. (2001). The LD4 motif of paxillin regulates cell spreading and motility through an interaction with paxillin kinase linker (PKL). Journal of Cell Biology, 154(1), 161–176.

    Article  PubMed  CAS  Google Scholar 

  72. Nayal, A., Webb, D. J., Brown, C. M., Schaefer, E. M., Vicente-Manzanares, M., & Horwitz, A. R. (2006). Paxillin phosphorylation at Ser273 localizes a GIT1–PIX–PAK complex and regulates adhesion and protrusion dynamics. Journal of Cell Biology, 173(4), 587–589.

    Article  PubMed  CAS  Google Scholar 

  73. 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(4), 851–863.

    Article  PubMed  CAS  Google Scholar 

  74. Lamorte, L., Rodrigues, S., Sangwan, V., Turner, C. E., & Park, M. (2003). Crk associates with a multimolecular paxillin/GIT2/beta-PIX complex and promotes Rac-dependent relocalization of paxillin to focal contacts. Molecular Biology of the Cell, 14(7), 2818–2831.

    Article  PubMed  CAS  Google Scholar 

  75. Shen, Y., Lyons, P., Cooley, M., Davidson, D., Veillette, A., Salgia, R., et al. (2000). The noncatalytic domain of protein–tyrosine phosphatase–PEST targets paxillin for dephosphorylation in vivo. Journal of Biological Chemistry, 275(2), 1405–1413.

    Article  PubMed  CAS  Google Scholar 

  76. Sastry, S. K., Lyons, P. D., Schaller, M. D., & Burridge, K. (2002). PTP–PEST controls motility through regulation of Rac1. Journal of Cell Science, 115(Pt 22), 4305–4316.

    Article  PubMed  CAS  Google Scholar 

  77. Jamieson, J. S., Tumbarello, D. A., Hallé, M., Brown, M. C., Tremblay, M. L., & Turner, C. E. (2005). Paxillin is essential for PTP–PEST-dependent regulation of cell spreading and motility: a role for paxillin kinase linker. Journal of Cell Science, 118(Pt 24), 5835–5847.

    Article  PubMed  CAS  Google Scholar 

  78. Griner, E. M., & Kazanietz, M. G. (2007). Protein kinase C and other diacylglycerol effectors in cancer. Nature Reviews Cancer, 7(4), 281–294.

    Article  PubMed  CAS  Google Scholar 

  79. Wu, W. S. (2006). The signaling mechanism of ROS in tumor progression. Cancer and Metastasis Reviews, 25(4), 695–705.

    Article  PubMed  CAS  Google Scholar 

  80. Lipscomb, E. A., & Mercurio, A. M. (2005). Mobilization and activation of a signaling competent alpha6beta4integrin underlies its contribution to carcinoma progression. Cancer and Metastasis Reviews, 24(3), 413–423.

    Article  PubMed  CAS  Google Scholar 

  81. Oka, M., & Kikkawa, U. (2005). Protein kinase C in melanoma. Cancer and Metastasis Reviews, 24(2), 287–300.

    Article  PubMed  CAS  Google Scholar 

  82. Kiley, S. C., Clark, K. J., Goodnough, M., Welch, D. R., & Jaken, S. (1999). Protein kinase C delta involvement in mammary tumor cell metastasis. Cancer Research, 59(13), 3230–3238.

    PubMed  CAS  Google Scholar 

  83. Pan, Q., Bao, L. W., Kleer, C. G., Sabel, M. S., Griffith, K. A., Teknos, T. N., et al. (2005). Protein kinase C epsilon is a predictive biomarker of aggressive breast cancer and a validated target for RNA interference anticancer therapy. Cancer Research, 65(18), 8366–8371.

    Article  PubMed  CAS  Google Scholar 

  84. Gopalakrishna, R., & Jaken, S. (2000). Protein kinase C signaling and oxidative stress. Free Radical Biology & Medicine, 28(9), 1349–1361.

    Article  CAS  Google Scholar 

  85. Gomez, D. E., Skilton, G., Alonso, D. F., & Kazanietz, M. G. (1999). The role of protein kinase C and novel phorbol ester receptors in tumor cell invasion and metastasis (review). Oncology Reports, 6(6), 1363–1370.

    PubMed  CAS  Google Scholar 

  86. Guan, C. X., Cui, Y. R., Zhang, M., Bai, H. B., Khunkhun, R., & Fang, X. (2007). Intracellular signaling molecules involved in vasoactive intestinal peptide-mediated wound healing in human bronchial epithelial cells. Peptides, 28(9), 1667–1673.

    Article  PubMed  CAS  Google Scholar 

  87. Keshamouni, V. G., Mattingly, R. R., & Reddy, K. B. (2002). Mechanism of 17-beta-estradiol-induced Erk1/2 activation in breast cancer cells. A role for HER2 AND PKC-delta. Journal of Biological Chemistry, 277(25), 22558–22565.

    Article  PubMed  CAS  Google Scholar 

  88. Besson, A., Davy, A., Robbins, S. M., & Yong, V. W. (2001). Differential activation of ERKs to focal adhesions by PKC epsilon is required for PMA-induced adhesion and migration of human glioma cells. Oncogene, 20(50), 7398–7407.

    Article  PubMed  CAS  Google Scholar 

  89. Pukac, L., Huangpu, J., & Karnovsky, M. J. (1998). Platelet-derived growth factor-BB, insulin-like growth factor-I, and phorbol ester activate different signaling pathways for stimulation of vascular smooth muscle cell migration. Experimental Cell Research, 242(2), 548–560.

    Article  PubMed  CAS  Google Scholar 

  90. Rigot, V., Lehmann, M., Andre, F., Daemi, N., Marvaldi, J., & Luis, J. (1998). Integrin ligation and PKC activation are required for migration of colon carcinoma cells. Journal of Cell Science, 111(Pt 20), 3119–3127.

    PubMed  CAS  Google Scholar 

  91. Larsson, C. (2006). Protein kinase C and the regulation of the actin cytoskeleton. Cellular Signalling, 18(3), 276–284.

    Article  PubMed  CAS  Google Scholar 

  92. Disatnik, M. H., & Rando, T. A. (1999). Integrin-mediated muscle cell spreading. The role of protein kinase C in outside-in and inside-out signaling and evidence of integrin cross-talk. Journal of Biological Chemistry, 274(45), 32486–32492.

    Article  PubMed  CAS  Google Scholar 

  93. Rabinovitz, I., Tsomo, L., & Mercurio, A. M. (2004). Protein kinase C-alpha phosphorylation of specific serines in the connecting segment of the beta 4 integrin regulates the dynamics of type II hemidesmosomes. Molecular and Cellular Biology, 24(10), 4351–4360.

    Article  PubMed  CAS  Google Scholar 

  94. Parsons, M., Keppler, M. D., Kline, A., Messent, A., Humphries, M. J., Gilchrist, R., et al. (2002). Site-directed perturbation of protein kinase C- integrin interaction blocks carcinoma cell chemotaxis. Molecular and Cellular Biology, 22(16), 5897–5911.

    Article  PubMed  CAS  Google Scholar 

  95. Nomura, N., Nomura, M., Sugiyama, K., & Hamada, J. (2007). Src regulates phorbol 12-myristate 13-acetate-activated PKC-induced migration via Cas/Crk/Rac1 signaling pathway in glioblastoma cells. International Journal of Molecular Medicine, 20(4), 511–519.

    PubMed  CAS  Google Scholar 

  96. Lee, M. S., Kim, Y. B., Lee, S. Y., Kim, J. G., Kim, S. H., Ye, S. K., et al. (2006). Integrin signaling and cell spreading mediated by phorbol 12-myristate 13-acetate treatment. Journal of Cellular Biochemistry, 99(1), 88–95.

    Article  PubMed  CAS  Google Scholar 

  97. De Nichilo, M. O., & Yamada, K. M. (1996). Integrin alpha v beta 5-dependent serine phosphorylation of paxillin in cultured human macrophages adherent to vitronectin. Journal of Biological Chemistry, 271(18), 11016–11022.

    Article  PubMed  Google Scholar 

  98. Doan, A. T., & Huttenlocher, A. (2007). RACK1 regulates Src activity and modulates paxillin dynamics during cell migration. Experimental Cell Research, 313(12), 2667–2679.

    Article  PubMed  CAS  Google Scholar 

  99. Poli, G., Leonarduzzi, G., Biasi, F., & Chiarpotto, E. (2004). Oxidative stress and cell signalling. Current Medicinal Chemistry, 11(9), 1163–1182.

    PubMed  CAS  Google Scholar 

  100. Aslan, M., & Ozben, T. (2003). Oxidants in receptor tyrosine kinase signal transduction pathways. Antioxidants & Redox Signalling, 5(6), 781–788.

    Article  CAS  Google Scholar 

  101. Chiarugi, P. (2005). PTPs versus PTKs: the redox side of the coin. Free Radical Research, 39(4), 353–364.

    Article  PubMed  CAS  Google Scholar 

  102. Giles, G. I. (2006). The redox regulation of thiol dependent signaling pathways in cancer. Current Pharmaceutical Design, 12(34), 4427–4443.

    Article  PubMed  CAS  Google Scholar 

  103. Chandel, N. S., & Budinger, G. R. (2007). The cellular basis for diverse responses to oxygen. Free Radical Biology & Medicine, 42(2), 165–174.

    Article  CAS  Google Scholar 

  104. Pervaiz, S. (2006). Pro-oxidant milieu blunts scissors: insight into tumor progression, drug resistance, and novel druggable targets. Current Pharmaceutical Design, 12(34), 4469–4477.

    Article  PubMed  CAS  Google Scholar 

  105. Cheng, G. C., Schulze, P. C., Lee, R. T., Sylvan, J., Zetter, B. R., & Huang, H. (2004). Oxidative stress and thioredoxin-interacting protein promote intravasation of melanoma cells. Experimental Cell Research, 300(2), 297–307.

    Article  PubMed  CAS  Google Scholar 

  106. Ferraro, D., Corso, S., Fasano, E., Panieri, E., Santangelo, R., Borrello, S., et al. (2006). Pro-metastatic signaling by c-Met through RAC-1 and reactive oxygen species (ROS). Oncogene, 25(26), 3689–3698.

    Article  PubMed  CAS  Google Scholar 

  107. Park, I. J., Hwang, J. T., Kim, Y. M., Ha, J., & Park, O. J. (2006). Differential modulation of AMPK signaling pathways by low or high levels of exogenous reactive oxygen species in colon cancer cells. Annals of the New York Academy of Sciences, 1091, 102–109.

    Article  PubMed  CAS  Google Scholar 

  108. Jagadeeswaran, R., Jagadeeswaran, S., Bindokas, V. P., & Salgia, R. (2007). Activation of HGF/c-Met pathway contributes to the reactive oxygen species generation and motility of small cell lung cancer cells. American Journal of Physiology Lung Cellular and Molecular Physiology, 292(6), L1488–1494.

    Article  PubMed  CAS  Google Scholar 

  109. Nishigori, C., Hattori, Y., & Toyokuni, S. (2004). Role of reactive oxygen species in skin carcinogenesis. Antioxidants & Redox Signalling, 6(3), 561–570.

    Article  CAS  Google Scholar 

  110. Miura, D., Miura, Y., & Yagasaki, K. (2004). Resveratrol inhibits hepatoma cell invasion by suppressing gene expression of hepatocyte growth factor via its reactive oxygen species-scavenging property. Clinical & Experimental Metastasis, 21(5), 445–451.

    Article  CAS  Google Scholar 

  111. Nimnual, A. S., Taylor, L. J., & Bar-Sagi, D. (2003). Redox-dependent downregulation of Rho by Rac. Nature Cell Biology, 5(3), 236–241.

    Article  PubMed  CAS  Google Scholar 

  112. Voncken, J. W., van Schaick, H., Kaartinen, V., Deemer, K., Coates, T., Landing, B., et al. (1995). Increased neutrophil respiratory burst in bcr-null mutants. Cell, 80(5), 719–728.

    Article  PubMed  CAS  Google Scholar 

  113. Bokoch, G. M., & Knaus, U. G. (2003). NADPH oxidases: not just for leukocytes anymore!. Trends in Biochemical Sciences, 28(9), 502–508.

    Article  PubMed  CAS  Google Scholar 

  114. Choi, M. H., Lee, I. K., Kim, G. W., Kim, B. U., Han, Y. H., Yu, D. Y., et al. (2005). Regulation of PDGF signalling and vascular remodelling by peroxiredoxin II. Nature, 435(7040), 347–353.

    Article  PubMed  CAS  Google Scholar 

  115. Arakaki, N., Kajihara, T., Arakaki, R., Ohnishi, T., Kazi, J. A., Nakashima, H., et al. (1999). Involvement of oxidative stress in tumor cytotoxic activity of hepatocyte growth factor/scatter factor. Journal of Biological Chemistry, 274(19), 13541–13546.

    Article  PubMed  CAS  Google Scholar 

  116. Colavitti, R., Pani, G., Bedogni, B., Anzevino, R., Borrello, S., Waltenberger, J., et al. (2002). Reactive oxygen species as downstream mediators of angiogenic signaling by vascular endothelial growth factor receptor-2/KDR. Journal of Biological Chemistry, 277(5), 3101–3108.

    Article  PubMed  CAS  Google Scholar 

  117. Werner, E., & Werb, Z. (2002). Integrins engage mitochondrial function for signal transduction by a mechanism dependent on Rho GTPases. Journal of Biological Chemistry, 158(2), 357–368.

    CAS  Google Scholar 

  118. Kamata, H., Honda, S., Maeda, S., Chang, L., Hirata, H., & Karin, M. (2005). Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell, 120(5), 649–661.

    Article  PubMed  CAS  Google Scholar 

  119. Chen, C. C., Young, J. L., Monzon, R. I., Chen, N., Todorovic, V., & Lau, L. F. (2007). Cytotoxicity of TNFalpha is regulated by integrin-mediated matrix signaling. EMBO Journal, 26(5), 1257–1267.

    Article  PubMed  CAS  Google Scholar 

  120. Chiarugi, P. (2003). Reactive oxygen species as mediators of cell adhesion. Italian Journal of Biochemistry, 52(1), 28–32.

    PubMed  CAS  Google Scholar 

  121. Chiarugi, P., Pani, G., Giannoni, E., Taddei, L., Colavitti, R., Raugei, G., et al. (2003). Reactive oxygen species as essential mediators of cell adhesion: the oxidative inhibition of a FAK tyrosine phosphatase is required for cell adhesion. Journal of Cell Biology, 161(5), 933–944.

    Article  PubMed  CAS  Google Scholar 

  122. Choi, M. H., Lee, I. K., Kim, G. W., Kim, B. U., Han, Y. H., Yu, D. Y., et al. (2005). Regulation of PDGF signalling and vascular remodelling by peroxiredoxin II. Nature, 435(7040), 347–353.

    Article  PubMed  CAS  Google Scholar 

  123. Meng, T. C., Fukada, T., & Tonks, N. K. (2002). Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo. Molecular Cell, 9(2), 387–399.

    Article  PubMed  CAS  Google Scholar 

  124. Lee, J. K., Edderkaoui, M., Truong, P., Ohno, I., Jang, K. T., Berti, A., et al. (2007). NADPH oxidase promotes pancreatic cancer cell survival via inhibiting JAK2 dephosphorylation by tyrosine phosphatases. Gastroenterology, 133(5), 1637–1648.

    Article  PubMed  CAS  Google Scholar 

  125. Gozin, A., Franzini, E., Andrieu, V., Da Costa, L., Rollet-Labelle, E., & Pasquier, C. (1998). Reactive oxygen species activate focal adhesion kinase, paxillin and p130cas tyrosine phosphorylation in endothelial cells. Free Radical Biology & Medicine, 25(9), 1021–1032.

    Article  CAS  Google Scholar 

  126. Ushio-Fukai, M., Tang, Y., Fukai, T., Dikalov, S. I., Ma, Y., Fujimoto, M., et al. (2002). Novel role of gp91(phox) containing NAD(P)H oxidase in vascular endothelial growth factor-induced signaling and angiogenesis. Circulation Research, 91(12), 1160–1167.

    Article  PubMed  CAS  Google Scholar 

  127. Wu, R. F., Xu, Y. C., Ma, Z., Nwariaku, F. E., Sarosi Jr, G. A., & Terada, L. S. (2005). Subcellular targeting of oxidants during endothelial cell migration. Journal of Cell Biology, 171(5), 893–904.

    Article  PubMed  CAS  Google Scholar 

  128. Xu, Y. C., Wu, R. F., Gu, Y., Yang, Y. S., Yang, M. C., Nwariaku, F. E., et al. (2002). Involvement of TRAF4 in oxidative activation of c-Jun N-terminal kinase. Journal of Biological Chemistry, 277(31), 28051–28057.

    Article  PubMed  CAS  Google Scholar 

  129. Zhang, J., Zhang, L. X., Meltzer, P. S., Barrett, J. C., & Trent, J. M. (2000). Molecular cloning of human Hic-5, a potential regulator involved in signal transduction and cellular senescence. Molecular Carcinogenesis, 27(3), 177–183.

    Article  PubMed  CAS  Google Scholar 

  130. 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(4), 851–863.

    Article  PubMed  CAS  Google Scholar 

  131. Matsuya, M., Sasaki, H., Aoto, H., Mitaka, T., Nagura, K., Ohba, T., et al. (1998). Cell adhesion kinase beta forms a complex with a new member, Hic-5, of proteins localized at focal adhesions. Journal of Biological Chemistry, 273(2), 1003–1014.

    Article  PubMed  CAS  Google Scholar 

  132. Nishiya, N., Iwabuchi, Y., Shibanuma, M., Côté, J. F., Tremblay, M. L., & Nose, K. (1999). Hic-5, a paxillin homologue, binds to the protein-tyrosine phosphatase PEST (PTP–PEST) through its LIM 3 domain. Journal of Biological Chemistry, 274(14), 9847–9853.

    Article  PubMed  CAS  Google Scholar 

  133. Lee, K., & Esselman, W. J. (2002). Inhibition of PTPs by H(2)O(2) regulates the activation of distinct MAPK pathways. Free Radical Biology & Medicine, 33(8), 1121–1132.

    Article  CAS  Google Scholar 

  134. Greene, E. L., Lu, G., Zhang, D., & Egan, B. M. (2001). Signaling events mediating the additive effects of oleic acid and angiotensin II on vascular smooth muscle cell migration. Hypertension, 37(2), 308–312.

    PubMed  CAS  Google Scholar 

  135. Gopalakrishna, R., & Jaken, S. (2000). Protein kinase C signaling and oxidative stress. Free Radical Biology & Medicine, 28(9), 1349–1361.

    Article  CAS  Google Scholar 

  136. Shackelford, R. E., Kaufmann, W. K., & Paules, R. S. (2000). Oxidative stress and cell cycle checkpoint function. Free Radical Biology & Medicine, 28(9), 1387–1404.

    Article  CAS  Google Scholar 

  137. Lin, D., & Takemoto, D. J. (2005). Oxidative activation of protein kinase Cgamma through the C1 domain. Effects on gap junctions. Journal of Biological Chemistry, 280(14), 13682–13693.

    Article  PubMed  CAS  Google Scholar 

  138. Inoguchi, T., Sonta, T., Tsubouchi, H., Etoh, T., Kakimoto, M., Sonoda, N., et al. (2003). Protein kinase C-dependent increase in reactive oxygen species (ROS) production in vascular tissues of diabetes: role of vascular NAD(P)H oxidase. Journal of the American Society of Nephrology, 14(8 Suppl 3), S227–232.

    Article  PubMed  CAS  Google Scholar 

  139. Lee, H. B., Yu, M. R., Yang, Y., Jiang, Z., & Ha, H. (2003). Reactive oxygen species-regulated signaling pathways in diabetic nephropathy. Journal of The American Society of Nephrology, 14(8 Suppl 3), S241–245.

    Article  PubMed  CAS  Google Scholar 

  140. Frey, R. S., Gao, X., Javaid, K., Siddiqui, S. S., Rahman, A., & Malik, A. B. (2006). Phosphatidylinositol 3-kinase gamma signaling through protein kinase Czeta induces NADPH oxidase-mediated oxidant generation and NF-kappaB activation in endothelial cells. Journal of Biological Chemistry, 281(23), 16128–16138.

    Article  PubMed  CAS  Google Scholar 

  141. Kwan, J., Wang, H., Munk, S., Xia, L., Goldberg, H. J., & Whiteside, C. I. (2005). In high glucose protein kinase C-zeta activation is required for mesangial cell generation of reactive oxygen species. Kidney International, 68(6), 2526–2541.

    Article  PubMed  CAS  Google Scholar 

  142. Xia, L., Wang, H., Goldberg, H. J., Munk, S., Fantus, I. G., & Whiteside, C. I. (2006). Mesangial cell NADPH oxidase upregulation in high glucose is protein kinase C dependent and required for collagen IV expression. American Journal of Physiology, Renal Physiology, 290(2), F345–356.

    Article  CAS  Google Scholar 

  143. Talior, I., Tennenbaum, T., Kuroki, T., & Eldar-Finkelman, H. (2005). PKC-delta-dependent activation of oxidative stress in adipocytes of obese and insulin-resistant mice: role for NADPH oxidase. American Journal of Physiology: Endocrinology and Metabolism, 288(2), E405–411.

    Article  PubMed  CAS  Google Scholar 

  144. Lee, H. B., Yu, M. R., Song, J. S., & Ha, H. (2004). Reactive oxygen species amplify protein kinase C signaling in high glucose-induced fibronectin expression by human peritoneal mesothelial cells. Kidney International, 65(4), 1170–1179.

    Article  PubMed  CAS  Google Scholar 

  145. Takahashi, A., Ohtani, N., Yamakoshi, K., Iida, S., Tahara, H., Nakayama, K., et al. (2006). Mitogenic signalling and the p16INK4a-Rb pathway cooperate to enforce irreversible cellular senescence. Nature Cell Biology, 8(11), 1291–1297.

    Article  PubMed  CAS  Google Scholar 

  146. Chen, C. C. (1999). Protein kinase C alpha, delta, epsilon and zeta in C6 glioma cells. TPA induces translocation and down-regulation of conventional and new PKC isoforms but not atypical PKC zeta. FEBS Letters, 332(1–2), 169–173.

    Google Scholar 

Download references

Acknowledgement

We thank the financial support from National Science council in Taiwan for the studies relevant to ROS-mediated signal transduction.

Author information

Authors and Affiliations

  1. Department of Medical Technology, Tzu Chi University, No. 701, Chung Yang Rd, Sec 3, Hualien, 970, Taiwan

    Wen-Sheng Wu & Jia-Ru Wu

  2. Graduate Institute of Medicine, Tzu Chi University, Hualien, Taiwan

    Wen-Sheng Wu & Jia-Ru Wu

  3. Research Centre for Hepatology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan

    Chi-Tan Hu

Authors
  1. Wen-Sheng Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jia-Ru Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chi-Tan Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wen-Sheng Wu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wu, WS., Wu, JR. & Hu, CT. Signal cross talks for sustained MAPK activation and cell migration: the potential role of reactive oxygen species. Cancer Metastasis Rev 27, 303–314 (2008). https://doi.org/10.1007/s10555-008-9112-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10555-008-9112-4

Keywords

Search

Navigation