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http://dx.doi.org/10.7314/APJCP.2012.13.6.2897

Mda-9/syntenin Promotes Human Brain Glioma Migration through Focal Adhesion Kinase (FAK)-JNK and FAK-AKT Signaling  

Zhong, Dong (Department of Neurosurgery, The 1st Affiliated Hospital)
Ran, Jian-Hua (Neuroscience Research Center, Chongqing University of Medical Sciences)
Tang, Wen-Yuan (Department of Neurosurgery, The 1st Affiliated Hospital)
Zhang, Xiao-Dong (Department of Neurosurgery, The 1st Affiliated Hospital)
Tan, Yun (Department of Neurosurgery, The 1st Affiliated Hospital)
Chen, Gui-Jie (Department of Neurosurgery, The 1st Affiliated Hospital)
Li, Xiao-Song (Neuroscience Research Center, Chongqing University of Medical Sciences)
Yan, Yi (Department of Neurosurgery, The 1st Affiliated Hospital)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.13, no.6, 2012 , pp. 2897-2901 More about this Journal
Abstract
Invasion is usually recognized as the main reason for the high recurrence and death rates of glioma and restricts the efficacy of surgery and other therapies. Therefore, we aimed to investigate the mechanism involved in promotion effects of mda-9/syntenin on human glioma cell migration. The wound healing method was used to test the migration ability of human glioma cells CHG-5 and CHG-hS, stably overexpressing mda-9/syntenin. Western blotting was performed to determine the expression and phosphorylation of focal adhesion kinase (FAK) and JNK in CHG-5 and CHG-hS cells. The migration ability of CHG-hS cells was significantly higher than that of CHG-5 cells in fibronectin (FN)-coated culture plates. Phosphorylation of FAK on tyrosine 397, 576, and 925 sites was increased with time elapsed in CHG-hS cells. However, phosphorylated FAK on the tyrosine 861 site was not changed. Phosphorylated Src, JNK and Akt levels in CHG-hS cells were also significantly upregulated. Phosphorylation of JNK and Akt were abolished by the specific inhibitors SP600125 and LY294002, respectively, and the migration ability of CHG-hS cells was decreased, indicating that the JNK and PI3K/Akt pathways play important roles in regulating mda-9/syntenin-induced human brain glioma migration. Our results indicate Mda-9/syntenin overexpression could activate FAK-JNK and FAK-Akt signaling and then enhance the migration capacity of human brain glioma cells.
Keywords
Glioma; mda-9/syntenin; focal adhesion kinase; migration;
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1 Helmke BM, Polychronidis M, Benner A, et al (2004). Melanoma metastasis is associated with enhanced expression of the syntenin gene. Oncol Rep, 12, 221-8.
2 Hirbec H, Martin S, Henley JM (2005). Syntenin is involved in the developmental regulation of neuronal membrane architecture. Mol Cell Neurosci, 28, 737-46.   DOI
3 Akasaka T, van Leeuwen RL, Yoshinaga IG, Mihm MC, Jr., Byers HR (1995). Focal adhesion kinase (p125FAK) expression correlates with motility of human melanoma cell lines. J Invest Dermatol, 105, 104-8.   DOI
4 Beekman JM, Coffer PJ (2008). The ins and outs of syntenin, a multifunctional intracellular adaptor protein. J Cell Sci, 121, 1349-55   DOI
5 Boukerche H, Aissaoui H, Prevost C, et al (2010). Src kinase activation is mandatory for MDA-9/syntenin-mediated activation of nuclear factor-kappaB. Oncogene, 29, 3054-66.   DOI
6 Boukerche H, Su ZZ, Emdad L, et al (2005). mda-9/Syntenin: a positive regulator of melanoma metastasis. Cancer Res, 65, 10901-11.   DOI
7 Jing C, Yuan L, Xingguo P, et al (2011). Promising fusion protein design to target the U87 MG glioma cell line. Asian Pac J Cancer Prev, 12, 935-7.
8 Zimmermann P, Tomatis D, Rosas M, et al (2001). Characterization of syntenin, a syndecan-binding PDZ protein, as a component of cell adhesion sites and microfilaments. Mol Biol Cell, 12, 339-50.   DOI   ScienceOn
9 Hwangbo C, Kim J, Lee JJ, Lee JH Activation of the integrin effector kinase focal adhesion kinase in cancer cells is regulated by crosstalk between protein kinase Calpha and the PDZ adapter protein mda-9/Syntenin. Cancer Res, 70, 1645-55.   DOI
10 Hwangbo C, Kim J, Lee JJ, Lee JH (2010). Activation of the integrin effector kinase focal adhesion kinase in cancer cells is regulated by crosstalk between protein kinase Calpha and the PDZ adapter protein mda-9/Syntenin. Cancer Res, 70, 1645-55.   DOI
11 Mitra SK, Hanson DA, Schlaepfer DD (2005). Focal adhesion kinase: in command and control of cell motility. Nat Rev Mol Cell Biol, 6, 56-68.   DOI
12 Koo TH, Lee JJ, Kim EM, et al (2002). Syntenin is overexpressed and promotes cell migration in metastatic human breast and gastric cancer cell lines. Oncogene, 21, 4080-8.   DOI
13 Lin JJ, Jiang H, Fisher PB (1998). Melanoma differentiation associated gene-9, mda-9, is a human gamma interferon responsive gene. Gene, 207, 105-10.   DOI
14 Meurice N, Wang L, Lipinski CA, et al (2010). Structural conservation in band 4.1, ezrin, radixin, moesin (FERM) domains as a guide to identify inhibitors of the proline-rich tyrosine kinase 2. J Med Chem, 53, 669-77.   DOI
15 Rondepierre F, Bouchon B, Bonnet M, et al (2010). B16 melanoma secretomes and in vitro invasiveness: syntenin as an invasion modulator. Melanoma Res, 20, 77-84.   DOI
16 Nakada M, Nakada S, Demuth T, et al (2007). Molecular targets of glioma invasion. Cell Mol Life Sci, 64, 458-78.   DOI
17 Owens LV, Xu L, Craven RJ, et al (1995). Overexpression of the focal adhesion kinase (p125FAK) in invasive human tumors. Cancer Res, 55, 2752-5.
18 Richardson A, Parsons T (1996). A mechanism for regulation of the adhesion-associated proteintyrosine kinase pp125FAK. Nature, 380, 538-40.   DOI
19 Salhia B, Tran NL, Symons M, et al (2006). Molecular pathways triggering glioma cell invasion. Expert Rev Mol Diagn, 6, 613-26.   DOI
20 Sarkar D, Boukerche H, Su ZZ, Fisher PB (2008). mda-9/ Syntenin: more than just a simple adapter protein when it comes to cancer metastasis. Cancer Res, 68, 3087-93.   DOI
21 Wen PY, Kesari S (2008). Malignant gliomas in adults. N Engl J Med, 359, 492-507.   DOI
22 Sulka B, Lortat-Jacob H, Terreux R, Letourneur F, Rousselle P (2009). Tyrosine dephosphorylation of the syndecan-1 PDZ binding domain regulates syntenin-1 recruitment. J Biol Chem, 284, 10659-71.   DOI
23 Thomas SM, Brugge JS (1997). Cellular functions regulated by Src family kinases. Annu Rev Cell Dev Biol, 13, 513-609.   DOI   ScienceOn
24 Wang H, Yuan X, Zhou Z, et al (2011). MicroRNAs might be promising biomarkers of human gliomas. Asian Pac J Cancer Prev, 12, 833-5.
25 Yarrow JC, Perlman ZE, Westwood NJ, Mitchison TJ (2004). A high-throughput cell migration assay using scratch wound healing, a comparison of image-based readout methods. BMC Biotechnol, 4, 21.   DOI
26 Du J, Cheng B, Zhu X, Ling C (2011). Ginsenoside rg1, a novel glucocorticoid receptor agonist of plant origin, maintains glucocorticoid efficacy with reduced side effects. J Immunol, 187, 942-50.   DOI
27 Boukerche H, Su ZZ, Emdad L, Sarkar D, Fisher PB (2007). mda-9/Syntenin regulates the metastatic phenotype in human melanoma cells by activating nuclear factor-kappaB. Cancer Res, 67, 1812-22.   DOI
28 Boukerche H, Su ZZ, Prevot C, Sarkar D, Fisher PB (2008). mda- 9/Syntenin promotes metastasis in human melanoma cells by activating c-Src. Proc Natl Acad Sci USA, 105, 15914-9.   DOI
29 Cary LA, Chang JF, Guan JL (1996). Stimulation of cell migration by overexpression of focal adhesion kinase and its association with Src and Fyn. J Cell Sci, 109 (Pt 7), 1787-94.