DOI QR코드

DOI QR Code

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

  • Zhong, Dong ;
  • Ran, Jian-Hua ;
  • Tang, Wen-Yuan ;
  • Zhang, Xiao-Dong ;
  • Tan, Yun ;
  • Chen, Gui-Jie ;
  • Li, Xiao-Song ;
  • Yan, Yi
  • Published : 2012.06.30

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

References

  1. 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. https://doi.org/10.1111/1523-1747.ep12313396
  2. Beekman JM, Coffer PJ (2008). The ins and outs of syntenin, a multifunctional intracellular adaptor protein. J Cell Sci, 121, 1349-55 https://doi.org/10.1242/jcs.026401
  3. 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. https://doi.org/10.1038/onc.2010.65
  4. Boukerche H, Su ZZ, Emdad L, et al (2005). mda-9/Syntenin: a positive regulator of melanoma metastasis. Cancer Res, 65, 10901-11. https://doi.org/10.1158/0008-5472.CAN-05-1614
  5. 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. https://doi.org/10.1158/0008-5472.CAN-06-3875
  6. 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. https://doi.org/10.1073/pnas.0808171105
  7. 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.
  8. 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. https://doi.org/10.4049/jimmunol.1002579
  9. 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.
  10. Hirbec H, Martin S, Henley JM (2005). Syntenin is involved in the developmental regulation of neuronal membrane architecture. Mol Cell Neurosci, 28, 737-46. https://doi.org/10.1016/j.mcn.2004.12.005
  11. 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. https://doi.org/10.1158/0008-5472.CAN-09-2447
  12. 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. https://doi.org/10.1158/0008-5472.CAN-09-2447
  13. 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.
  14. 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. https://doi.org/10.1038/sj.onc.1205514
  15. 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. https://doi.org/10.1016/S0378-1119(97)00562-3
  16. 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. https://doi.org/10.1021/jm901247a
  17. 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. https://doi.org/10.1038/nrm1549
  18. Nakada M, Nakada S, Demuth T, et al (2007). Molecular targets of glioma invasion. Cell Mol Life Sci, 64, 458-78. https://doi.org/10.1007/s00018-007-6342-5
  19. 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.
  20. Richardson A, Parsons T (1996). A mechanism for regulation of the adhesion-associated proteintyrosine kinase pp125FAK. Nature, 380, 538-40. https://doi.org/10.1038/380538a0
  21. 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. https://doi.org/10.1097/CMR.0b013e32833279f2
  22. Salhia B, Tran NL, Symons M, et al (2006). Molecular pathways triggering glioma cell invasion. Expert Rev Mol Diagn, 6, 613-26. https://doi.org/10.1586/14737159.6.4.613
  23. 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. https://doi.org/10.1158/0008-5472.CAN-07-6210
  24. 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. https://doi.org/10.1074/jbc.M807643200
  25. Thomas SM, Brugge JS (1997). Cellular functions regulated by Src family kinases. Annu Rev Cell Dev Biol, 13, 513-609. https://doi.org/10.1146/annurev.cellbio.13.1.513
  26. 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.
  27. Wen PY, Kesari S (2008). Malignant gliomas in adults. N Engl J Med, 359, 492-507. https://doi.org/10.1056/NEJMra0708126
  28. 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. https://doi.org/10.1186/1472-6750-4-21
  29. 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. https://doi.org/10.1091/mbc.12.2.339

Cited by

  1. Elevated expression of syntenin in breast cancer is correlated with lymph node metastasis and poor patient survival vol.15, pp.3, 2013, https://doi.org/10.1186/bcr3442
  2. MDA-9/syntenin is a key regulator of glioma pathogenesis vol.16, pp.1, 2013, https://doi.org/10.1093/neuonc/not157
  3. MicroRNA-16 suppresses epithelial-mesenchymal transition-related gene expression in human glioma vol.10, pp.6, 2014, https://doi.org/10.3892/mmr.2014.2583
  4. Staurosporine Induced Apoptosis Rapidly Downregulates TDP-43 in Glioma Cells vol.15, pp.8, 2014, https://doi.org/10.7314/APJCP.2014.15.8.3575
  5. The diverse roles and multiple forms of focal adhesion kinase in brain vol.40, pp.11, 2014, https://doi.org/10.1111/ejn.12737
  6. Targeting tumor invasion: the roles of MDA-9/Syntenin vol.19, pp.1, 2015, https://doi.org/10.1517/14728222.2014.959495
  7. Basic fibroblast growth factor promotes melanocyte migration via activating PI3K/Akt-Rac1-FAK-JNK and ERK signaling pathways vol.68, pp.9, 2016, https://doi.org/10.1002/iub.1531
  8. MDA-9/Syntenin Control vol.231, pp.3, 2015, https://doi.org/10.1002/jcp.25136
  9. Berberine Inhibits Human Melanoma A375.S2 Cell Migration and Invasion via Affecting the FAK, uPA, and NF-κB Signaling Pathways and Inhibits PLX4032 Resistant A375.S2 Cell Migration In Vitro vol.23, pp.8, 2018, https://doi.org/10.3390/molecules23082019
  10. Syntenin1/MDA-9 (SDCBP) induces immune evasion in triple-negative breast cancer by upregulating PD-L1 vol.171, pp.2, 2018, https://doi.org/10.1007/s10549-018-4833-8

Acknowledgement

Supported by : Natural Science Foundation of Chongqing