Browse > Article

CAGE, a Novel Cancer/Testis Antigen Gene, Promotes Cell Motility by Activating ERK and p38 MAPK and Downregulating ROS  

Shim, Hyeeun (School of Biological Sciences, College of Natural Sciences, Kangwon National University)
Shim, Eunsook (School of Biological Sciences, College of Natural Sciences, Kangwon National University)
Lee, Hansoo (School of Medicine, Kangwon National University)
Hahn, Janghee (Korea Basic Science Institute, Chunchon Center)
Kang, Dongmin (Laboratory of Radiation Effect, Division of Radiation Biology, Korea Institute of Radiological and Medical Sciences)
Lee, Yun-Sil (School of Biological Sciences, College of Natural Sciences, Kangwon National University)
Jeoung, Dooil (School of Biological Sciences, College of Natural Sciences, Kangwon National University)
Publication Information
Molecules and Cells / v.21, no.3, 2006 , pp. 367-375 More about this Journal
Abstract
We previously identified a novel cancer/testis antigen gene CAGE by screening cDNA expression libraries of human testis and gastric cancer cell lines with sera of gastric cancer patients. CAGE is expressed in many cancers and cancer cell lines, but not in normal tissues apart from the testis. In the present study, we investigated its role in the motility of cells of two human cancer cell lines: HeLa and the human hepatic cancer cell line, SNU387. Induction of CAGE by tetracycline or transient transfection enhanced the migration and invasiveness of HeLa cells, but not the adhesiveness of either cell line. Overexpression of CAGE led to activation of ERK and p38 MAPK but not Akt, and inhibition of ERK by PD98059 or p38 MAPK by SB203580 counteracted the CAGE-promoted increase in motility in both cell lines. Overexpression of CAGE also resulted in a reduction of ROS and an increase of ROS scavenging, associated with induction of catalase activity. Inhibition of ERK and p38 MAPK increased ROS levels in cells transfected with CAGE, suggesting that ROS reduce the motility of both cell lines. Inhibition of ERK and p38 MAPK reduced the induction of catalase activity resulting from overexpression of CAGE, and inhibition of catalase reduced CAGE-promoted motility. We conclude that CAGE enhances the motility of cancer cells by activating ERK and p38 MAPK, inducing catalase activity, and reducing ROS levels.
Keywords
CAGE; Catalase; ERK; Motility; p38 MAPK; ROS;
Citations & Related Records
Times Cited By KSCI : 3  (Citation Analysis)
Times Cited By Web Of Science : 11  (Related Records In Web of Science)
연도 인용수 순위
1 Desideri, G., Bravi, M. C., Tucci, M., Croce, G., Marinucci, M. C., et al. (2003) Angiotensin II inhibits endothelial cell motility through an AT1-dependent oxidant-sensitive decrement of nitric oxide availability. Arterioscler. Thromb. Vasc. Biol. 23, 1218-1223   DOI   ScienceOn
2 Huang, R. P., Wu, J. X., Fan, Y., and Adamson, E. D. (1996) UV activates growth factor receptors via reactive oxygen intermediates. J. Cell Biol. 133, 211-220   DOI   ScienceOn
3 Hwang, J.-J. and Hur, K. J. (2005) Insulin cannot activate extracellular- signal-related kinase due to inability to generate reactive oxygen species in SK-N-BE(2) human neuroblastoma cells. Mol. Cells 20, 280-287
4 Macip, S., Igarashi, M., Fang, L., Chen, A., Pan, Z. Q., et al. (2002) Inhibition of p21-mediated ROS accumulation can rescue p21-induced senescence. EMBO J. 21, 2180-2188   DOI   ScienceOn
5 Miura, D., Miura, Y., and Yagasaki, K. (2004) Resveratrol inhibits hepatoma cell invasion by suppressing gene expression of hepatocyte growth factor via its reactive oxygen speciesscavenging property. Clin. Exp. Metastasis 21, 445-451   DOI   ScienceOn
6 Park, M. J., Lee, J. Y., Kwak, H. J., Park, C. M., Lee, H. C., et al. (2005) Arsenic trioxide (As2O3) inhibits invasion of HT1080 human fibrosarcoma cells: role of nuclear factorkappaB and reactive oxygen species. J. Cell Biochem. 95, 955-969   DOI   ScienceOn
7 Shin, I., Kim, S., Song, H., Kim, H. R., and Moon, A. (2005) H-Ras-specific activation of Rac-MKK3/6-p38 pathway: its critical role in invasion and migration of breast epithelial cells. J. Biol. Chem. 280, 14675-14683   DOI   ScienceOn
8 Sossey-Alaoui, K., Ranalli, T. A., Li, X., Bakin, A. V., and Cowell, J. K. (2005) WAVE3 promotes cell motility and invasion through the regulation of MMP-1, MMP-3, and MMP-9 expression. Exp. Cell Res. 308, 135-145   DOI   ScienceOn
9 Tanaka, F., Fujie, T., Tahara, K., Mori, M., Takesako, K., et al. (1997) Induction of antitumor cytotoxic T lymphocytes with a MAGE-3-encoded synthetic peptide presented by human leukocytes antigen A-24. Cancer Res. 57, 4465-4468
10 Yamaoka-Tojo, M., Ushio-Fukai, M., Hilenski, L., Dikalov, S. I., Chen, Y. E., et al. (2004) IQGAP1, a novel vascular endothelial growth factor receptor binding protein, is involved in reactive oxygen species--dependent endothelial migration and proliferation. Circ. Res. 95, 276-283   DOI   ScienceOn
11 De Smet, C., Lurqun, C., Lethe, B., Martelange, V., and Boon, T. (1999) DNA methylation is the primary silencing mechanism for a set of germ line and tumor-specific genes with a CpG-rich promoter. Mol. Cell Biol. 19, 7327-7335   DOI
12 Boel, P. (1995) BAGE: A new gene encoding for an antigen recognized on human melanoma. Immunity 2, 167-175   DOI   ScienceOn
13 Boon, T. (1999) Tumor regression observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1. Int. J. Cancer 80, 219-230   DOI   ScienceOn
14 Sadanaga, N., Nagashima, H., Mashino, K., Tahara, K., Yamaguchi, H., et al. (2001) Dendritic cell vaccination with MAGE peptide is a novel therapeutic approach for gastrointestinal carcinoma. Cancer Res. 7, 2277-2284
15 Cho, B., Lee, H., Jeong, S., Bang, Y. J., Lee, H. J., et al. (2003) Promoter hypomethylation of a novel cancer/testis antigen gene CAGE is correlated with its aberrant expression and is seen in premalignant stage of gastric carcinoma. Biochem. Biophys. Res. Commun. 307, 52-63   DOI   ScienceOn
16 Sen, P., Chakraborty, P. K., and Raba, S. (2005) p38 mitogenactivated protein kinase (p38MAPK) upregulates catalase levels in response to low dose $H_2O_2$ treatment through enhancement of mRNA stability. FEBS Lett. 579, 4402-4406   DOI   ScienceOn
17 Chiarugi, P., Pani, G., Giannoni, E., Taddei, L., Colavitti, R., 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. J. Cell Biol. 161, 933-944   DOI   ScienceOn
18 Sundaresan, M., Yu, Z. X., Ferrans, V. J., Irani, K., and Finkel, T. (1995) Requirement for generation of H2O2 for plateletderived growth factor signal transduction. Science 270, 296-299   DOI   ScienceOn
19 Berglund, P., Stighall, M., Jirstrom, K., Borgquist, S., Sjolander, A., et al. (2005) Cyclin E overexpression obstructs infiltrative behavior in breast cancer: a novel role reflected in the growth pattern of medullary breast cancers. Cancer Res. 65, 9727-9234   DOI   ScienceOn
20 Coulie, P. G., Brichard, V., Van Pel, A., Wolfel, J., Schneider, J., et al. (1994) A new gene coding for a differentiation antigen recognized by autologous cytotoxic T Lymphocytes on HLAA2 melanomas. J. Exp. Med. 180, 35-42   DOI   ScienceOn
21 Urbich, C., Dernbach, E., Aicher, A., Zeiher, A. M., and Dimmeler, S. (2002) CD40 ligand inhibits endothelial cell migration by increasing production of endothelial reactive oxygen species. Circulation 106, 981-986   DOI   ScienceOn
22 Cho, B., Lim, Y., Lee, D. Y., Park, S. Y., Lee, H., et al. (2002) Identification and characterization of a novel cancer/testis antigen gene CAGE. Biochem. Biophys. Res. Commun. 292, 715-726   DOI   ScienceOn
23 De Backer, O., Arden, K. C., Boretti, M., Vantomme, V., De Smet, C., et al. (1999) Characterization of the GAGE genes that are expressed various human cancers and in normal testis. Cancer Res. 59, 3157-3165
24 Ho, W. C., Uniyal, S., Zhou, H., Morris, V. L., and Chan, B. M. (2005) Threshold levels of ERK activation for chemotactic migration differ for NGF and EGF in rat pheochromocytoma PC12 cells. Mol. Cell. Biochem. 271, 29-41   DOI
25 Ohba, M., Shibanuma, M., Kuroki, T., and Nose, K. (1994) Production of hydrogen peroxide by transforming growth factor-beta 1 and its involvement in induction of egr-1 in mouse osteoblastic cells. J. Cell Biol. 126, 1079-1088   DOI   ScienceOn
26 Bae, Y. S., Kang, S. W., Seo, M. S., Baines, I. C., Tekle, E., et al. (1997) Epidermal growth factor (EGF)-induced generation of hydrogen peroxide. Role in EGF receptor-mediated tyrosine phosphorylation. J. Biol. Chem. 272, 217-221   DOI   ScienceOn
27 Jager, E., Chen, Y. T., Drijfhout, J. W., Karbach, J., Ringhoffer, M., et al. (1998) Simultaneous humoral and immune response against cancer-testis antigen NY-ESO-1: definition of human histocompatibility leukocyte antigen (HLA-2)-A2-binding peptide epitopes. J. Exp. Med. 187, 265-270   DOI   ScienceOn
28 Liou, J. S., Chen, C. Y., Chen, J. S., and Faller, D. V. (2000) Oncogenic ras mediates apoptosis in response to protein kinase C inhibition through the generation of reactive oxygen species. J. Biol. Chem. 275, 39001-39011   DOI   ScienceOn
29 van den Bruggen, P., Travesari, C., Chomez, P., Lurquin, C., De Plaen, E., et al. (1991) A gene encoding an antigen recognized by cytolytic T lymphocytes. Science 254, 1643-1647   DOI
30 Lapointe, S. and Sirard, M. A. (1998) Catalase and oviductal fluid reverse the decreased motility of bovine sperm in culture medium containing specific amino acids. J. Androl. 19, 31-36
31 Domanico, S. Z., Pelletier, A. J., Havran, W. L., and Quaranta, V. (1997) Integrin alpha 6A beta 1 induces CD81-dependent cell motility without engaging the extracellular matrix migration substrate. Mol. Biol. Cell 8, 2253-2265   DOI
32 Chaux, P., Luiten, R., Demotte, N., Vantomm, V., Stroobant, V. C., et al. (1999) Identification of five MAGE-A1 epitopes recognized by cytolytic T lymphocytes obtained by in vitro stimulation with dendritic cells transduced with MAGEA1. J. Immunol. 163, 2928-2936
33 Pollock, C. B., Shirasawa, S., Sasazuki, T., Kolch, W., and Dhillon, A. S. (2005) Oncogenic K-RAS is required to maintain changes in cytoskeletal organization, adhesion, and motility in colon cancer cells. Cancer Res. 65, 1244-1250   DOI   ScienceOn
34 Weber, J., Salgaller, M., Samid, D., Johnson, B., Herlyn, M., et al. (1994) Expression of the MAGE1 tumor antigen is upregulated by the demethylating agent 5-aza-2′-deoxycytidine. Cancer Res. 54, 1766-1771
35 Brichard, V., Van Pel, A., Wolfel, T., Wolfel, C., De Plaen, E., et al. (1993) The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J. Exp. Med. 178, 489-495   DOI   ScienceOn
36 Kim, M. S., Lee, E. J., Kim, H. R., and Moon, A. (2003) p38 kinase is a key signaling molecule for H-Ras-induced cell motility and invasive phenotype in human breast epithelial cells. Cancer Res. 63, 5454-5461
37 Sattler, M., Verma, S., Shrikhande, G., Byrne, C. H., Pride, Y. B., et al. (2000) The BCR/ABL tyrosine kinase induces production of reactive oxygen species in hematopoietic cells. J. Biol. Chem. 275, 24273-24278   DOI   ScienceOn
38 Chen, Y. T., Gure, A. O., Tsang, S., Stockert, E., Jager, E., et al. (1998) Identification of multiple cancer/testis antigens by allogenic antibody screening of a melanoma cell line library. Proc. Natl. Acad. Sci. USA 95, 6919-6923
39 De Smet, C., De Backer, O., Faraoni, I., Lurquin, C., Brasseur, F., et al. (1996) The activation of human gene MAGE-1 in tumor cells is correlated with genome-wide demethylation. Proc. Natl. Acad. Sci. USA 93, 7149-7153
40 Benhar, M., Dalyot, I., Engelberg, D., and Levitzki, A. (2001) Enhanced ROS production in oncogenically transformed cells potentiates c-Jun N-terminal kinase and p38 mitogenactivated protein kinase activation and sensitization to genotoxic stress. Mol. Cell Biol. 21, 6913-6926   DOI   ScienceOn
41 Sonoda, Y., Aiba, N., Utsubo, R., Koguch, E., Hasegawa, M., et al. (2004) Induction of antioxidant enzymes by FAK in a human leukemic cell line HL-60. Biochim. Biophys. Acta 1683, 22-32   DOI
42 Lucas, S., De Smet, C., Arden, K. C., Viars, C. S., Lethe, B., et al. (1998) Identification of a new MAGE gene with tumorspecific expression by representational difference analysis. Cancer Res. 58, 743-752