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http://dx.doi.org/10.5352/JLS.2012.22.12.1621

Reactive Oxygen Species Mediates Lysophosphatidic Acid-induced Migration of SKOV-3 Ovarian Cancer Cells  

Kim, Eun Kyoung (MRC for Ischemic Tissue Regeneration, Medical Research Institute, Department of Pharmacology, Pusan National University School of Medicine)
Lee, Hye Sun (MRC for Ischemic Tissue Regeneration, Medical Research Institute, Department of Pharmacology, Pusan National University School of Medicine)
Ha, Hong Koo (Department of Urology, Pusan National University Hospital)
Yun, Sung Ji (MRC for Ischemic Tissue Regeneration, Medical Research Institute, Department of Pharmacology, Pusan National University School of Medicine)
Ha, Jung Min (MRC for Ischemic Tissue Regeneration, Medical Research Institute, Department of Pharmacology, Pusan National University School of Medicine)
Kim, Young Whan (MRC for Ischemic Tissue Regeneration, Medical Research Institute, Department of Pharmacology, Pusan National University School of Medicine)
Jin, In Hye (MRC for Ischemic Tissue Regeneration, Medical Research Institute, Department of Pharmacology, Pusan National University School of Medicine)
Shin, Hwa Kyoung (Department of Anatomy, Pusan National University School of Korean Medicine)
Bae, Sun Sik (MRC for Ischemic Tissue Regeneration, Medical Research Institute, Department of Pharmacology, Pusan National University School of Medicine)
Publication Information
Journal of Life Science / v.22, no.12, 2012 , pp. 1621-1627 More about this Journal
Abstract
Cell motility plays an essential role in many physiological responses, such as development, immune reaction, and angiogenesis. In the present study, we showed that lysophosphatidic acid (LPA) modulates cancer cell migration by regulation of generation of reactive oxygen species (ROS). Stimulation of SKOV-3 ovarian cancer cells with LPA strongly promoted migration. but this migration was completely blocked by pharmacological inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Inhibition of the ERK pathway had no effect on migration. Stimulation of SKOV-3 ovarian cancer cells with LPA significantly induced the generation of ROS in a time-dependent manner. LPA-induced generation of ROS was significantly blocked by pharmacological inhibition of PI3K or Akt, but inhibition of the ERK signaling pathway had little effect. LPA-induced generation of ROS was blocked by pretreatment of SKOV-3 ovarian cancer cells with an NADPH oxidase inhibitor, whereas inhibition of xanthine oxidase, cyclooxygenase, or mitochondrial respiratory chain complex I had no effect. Scavenging of ROS by N-acetylcysteine completely blocked LPA-induced migration of SKOV-3 ovarian cancer cells. Inhibition of NADPH oxidase blocked LPA-induced migration whereas inhibition of xanthine oxidase, cyclooxygenase, or mitochondrial respiratory chain complex I did not affect LPA-induced migration of SKOV-3 ovarian cancer cells. Given these results, we suggest that LPA induces ROS generation through the PI3K/Akt/NADPH oxidase signaling axis, thereby regulating cancer cell migration.
Keywords
Lysophosphatidic acid (LPA); reactive oxygen species (ROS); migration; NADPH oxidase; phosphatidylinositol 3-kinase (PI3K);
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1 Baumer, A. T., Ten Freyhaus, H., Sauer, H., Wartenberg, M., Kappert, K., Schnabel, P., Konkol, C., Hescheler, J., Vantler, M., and Rosenkranz, S. 2008. Phosphatidylinositol 3-kinase-dependent membrane recruitment of Rac-1 and p47phox is critical for ${\alpha}$-platelet-derived growth factor receptor-induced production of reactive oxygen species. J. Biol. Chem. 283, 7864-7876.   DOI
2 Bian, D., Su, S., Mahanivong, C., Cheng, R. K., Han, Q., Pan, Z. K., Sun, P., and Huang, S. 2004. Lysophosphatidic Acid Stimulates Ovarian Cancer Cell Migration via a Ras-MEK Kinase 1 Pathway. Cancer Res. 64, 4209-4217.   DOI
3 Chen, Q., Olashaw, N. and Wu, J. 1995. Participation of reactive oxygen species in the lysophosphatidic acid-stimulated mitogen-activated protein kinase kinase activation pathway. J. Biol. Chem. 270, 28499-28502.   DOI
4 Chiarugi, P. 2008. Src redox regulation: there is more than meets the eye. Mol. Cells 26, 329-337.   과학기술학회마을
5 Contos, J. J., Ishii, I. and Chun, J. 2000. Lysophosphatidic acid receptors. Mol. Pharmacol. 58, 1188-1196.
6 Dujardin, D. L., Barnhart, L. E., Stehman, S. A., Gomes, E. R., Gundersen, G. G. and Vallee, R. B. 2003. A role for cytoplasmic dynein and LIS1 in directed cell movement. J. Cell Biol. 163, 1205-1211.   DOI
7 Etienne-Manneville, S. and Hall, A. 2003. Cdc42 regulates GSK-3${\beta}$ and adenomatous polyposis coli to control cell polarity. Nature 421, 753-756.   DOI
8 Fishman, D. A., Liu, Y., Ellerbroek, S. M. and Stack, M. S. 2001. Lysophosphatidic acid promotes matrix metalloproteinase (MMP) activation and MMP-dependent invasion in ovarian cancer cells. Cancer Res. 61, 3194-3199.
9 Han, J., Luby-Phelps, K., Das, B., Shu, X., Xia, Y., Mosteller, R. D., Krishna, U. M., Falck, J. R., White, M. A. and Broek, D. 1998. Role of substrates and products of PI 3-kinase in regulating activation of Rac-related guanosine triphosphatases by Vav. Science 279, 558-560.   DOI
10 Hernandez-Negrete, I., Carretero-Ortega, J., Rosenfeldt, H., Hernandez-Garcia, R., Calderon-Salinas, J. V., Reyes-Cruz, G., Gutkind, J. S., and Vazquez-Prado, J. 2007. P-Rex1 links mammalian target of rapamycin signaling to Rac activation and cell migration. J. Biol. Chem. 282, 23708-23715.   DOI
11 Higuchi, M., Masuyama, N., Fukui, Y., Suzuki, A. and Gotoh, Y. 2001. Akt mediates Rac/Cdc42-regulated cell motility in growth factor-stimulated cells and in invasive PTEN knockout cells. Curr. Biol. 11, 1958-1962.   DOI
12 Hill, K., Krugmann, S., Andrews, S. R., Coadwell, W. J., Finan, P., Welch, H. C., Hawkins, P. T. and Stephens, L. R. 2005. Regulation of P-Rex1 by phosphatidylinositol (3,4,5)-trisphosphate and $G{\beta}{\gamma}$ subunits. J. Biol. Chem. 280, 4166-4173.   DOI
13 Huo, Y., Qiu, W. Y., Pan, Q., Yao, Y. F., Xing, K. and Lou, M. F. 2009. Reactive oxygen species (ROS) are essential mediators in epidermal growth factor (EGF)-stimulated corneal epithelial cell proliferation, adhesion, migration, and wound healing. Exp. Eye Res. 89, 876-886.   DOI
14 Imamura, F., Mukai, M., Ayaki, M., Takemura, K., Horai, T., Shinkai, K., Nakamura, H. and Akedo, H. 1999. Involvement of small GTPases Rho and Rac in the invasion of rat ascites hepatoma cells. Clin. Exp. Metastasis 17, 141-148.   DOI
15 Kim, E. K., Yun, S. J., Ha, J. M., Kim, Y. W., Jin, I. H., Woo, D. H., Lee, H. S., Ha, H. K. and Bae, S. S. 2012. Synergistic induction of cancer cell migration regulated by $G{\beta}{\gamma}$ and phosphatidylinositol 3-kinase. Exp. Mol. Med. 44, 483-491.   DOI
16 Kim, E. K., Yun, S. J., Ha, J. M., Kim, Y. W., Jin, I. H., Yun, J., Shin, H. K., Song, S. H., Kim, J. H., Lee, J. S., Kim, C. D. and Bae, S. S. 2011. Selective activation of Akt1 by mammalian target of rapamycin complex 2 regulates cancer cell migration, invasion, and metastasis. Oncogene 30, 2954-2963.   DOI
17 Maffucci, T., Cooke, F. T., Foster, F. M., Traer, C. J., Fry, M. J. and Falasca, M. 2005. Class II phosphoinositide 3-kinase defines a novel signaling pathway in cell migration. J. Cell Biol. 169, 789-799.   DOI
18 Koh, J. S., Lieberthal, W., Heydrick, S. and Levine, J. S. 1998. Lysophosphatidic acid is a major serum noncytokine survival factor for murine macrophages which acts via the phosphatidylinositol 3-kinase signaling pathway. J. Clinic. Invest. 102, 716-727.   DOI   ScienceOn
19 Lauffenburger, D. A. and Horwitz, A. F. 1996. Cell migration: a physically integrated molecular process. Cell 84, 359-369.   DOI   ScienceOn
20 Liou, G. Y. and Storz, P. 2010. Reactive oxygen species in cancer. Free Radic. Res. 44, 479-496.   DOI
21 Malchinkhuu, E., Sato, K., Horiuchi, Y., Mogi, C., Ohwada, S., Ishiuchi, S., Saito, N., Kurose, H., Tomura, H. and Okajima, F. 2005. Role of p38 mitogen-activated kinase and c-Jun terminal kinase in migration response to lysophosphatidic acid and sphingosine-1-phosphate in glioma cells. Oncogene 24, 6676-6688.   DOI
22 Meng, D., Lv, D. D. and Fang, J. 2008. Insulin-like growth factor-I induces reactive oxygen species production and cell migration through Nox4 and Rac1 in vascular smooth muscle cells. Cardiovasc. Res. 80, 299-308.   DOI
23 Oikawa, T., Yamaguchi, H., Itoh, T., Kato, M., Ijuin, T., Yamazaki, D., Suetsugu, S. and Takenawa, T. 2004. PtdIns(3,4,5)P3 binding is necessary for WAVE2-induced formation of lamellipodia. Nat. Cell Biol. 6, 420-426.   DOI
24 Panetti, T. S., Nowlen, J. and Mosher, D. F. 2000. Sphingosine-1-phosphate and lysophosphatidic acid stimulate endothelial cell migration. Arterioscler. Thromb. Vasc. Biol. 20, 1013-1019.   DOI
25 Ridley, A. J., Schwartz, M. A., Burridge, K., Firtel, R. A., Ginsberg, M. H., Borisy, G., Parsons, J. T. and Horwitz, A. R. 2003. Cell migration: integrating signals from front to back. Science 302, 1704-1709.   DOI
26 Pietruck, F., Busch, S., Virchow, S., Brockmeyer, N. and Siffert, W. 1997. Signalling properties of lysophosphatidic acid in primary human skin fibroblasts: role of pertussis toxin-sensitive GTP-binding proteins. Naunyn-Schmiedebergs Arch. Pharmacol. 355, 1-7.
27 Raftopoulou, M. and Hall, A. 2004. Cell migration: Rho GTPases lead the way. Dev. Biol. 265, 23-32.   DOI
28 Rhee, S. G., Kang, S. W., Jeong, W., Chang, T. S., Yang, K. S. and Woo, H. A. 2005. Intracellular messenger function of hydrogen peroxide and its regulation by peroxiredoxins. Curr. Opin. Cell Biol. 17, 183-189.   DOI
29 Russo, C., Gao, Y., Mancini, P., Vanni, C., Porotto, M., Falasca, M., Torrisi, M. R., Zheng, Y. and Eva, A. 2001. Modulation of oncogenic DBL activity by phosphoinositol phosphate binding to pleckstrin homology domain. J. Biol. Chem. 276, 19524-19531.   DOI
30 Sasaki, A. T., Chun, C., Takeda, K. and Firtel, R. A. 2004. Localized Ras signaling at the leading edge regulates PI3K, cell polarity, and directional cell movement. J. Cell Biol. 167, 505-518.   DOI
31 Saunders, J. A., Rogers, L. C., Klomsiri, C., Poole, L. B. and Daniel, L. W. 2010. Reactive oxygen species mediate lysophosphatidic acid induced signaling in ovarian cancer cells. Free Radic. Biol. Med. 49, 2058-2067.   DOI   ScienceOn
32 Shah, B. H., Neithardt, A., Chu, D. B., Shah, F. B. and Catt, K. J. 2006. Role of EGF receptor transactivation in phosphoinositide 3-kinase-dependent activation of MAP kinase by GPCRs. J. Cell. Physiol. 206, 47-57.   DOI
33 Welch, H. C., Coadwell, W. J., Ellson, C. D., Ferguson, G. J., Andrews, S. R., Erdjument-Bromage, H., Tempst, P., Hawkins, P. T. and Stephens, L. R. 2002. P-Rex1, a PtdIns(3,4,5)P3- and $G{\beta}{\gamma}$-regulated guanine-nucleotide exchange factor for Rac. Cell 108, 809-821.   DOI
34 Srinivasan, S., Wang, F., Glavas, S., Ott, A., Hofmann, F., Aktories, K., Kalman, D. and Bourne, H. R. 2003. Rac and Cdc42 play distinct roles in regulating PI(3,4,5)P3 and polarity during neutrophil chemotaxis. J. Cell Biol. 160, 375-385.   DOI
35 Weiner, O. D. 2002. Rac activation: P-Rex1 - a convergence point for PIP(3) and $G{\beta}{\gamma}$? Curr. Biol. 12, R429-431.   DOI
36 Weiner, O. D. 2002. Regulation of cell polarity during eukaryotic chemotaxis: the chemotactic compass. Curr. Opin. Cell Biol. 14, 196-202.   DOI
37 Xu, Y., Shen, Z., Wiper, D. W., Wu, M., Morton, R. E., Elson, P., Kennedy, A. W., Belinson, J., Markman, M. and Casey, G. 1998. Lysophosphatidic acid as a potential biomarker for ovarian and other gynecologic cancers. JAMA 280, 719-723.   DOI   ScienceOn