Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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14-3-3ζ Regulates Immune Response through Stat3 Signaling in Oral Squamous Cell Carcinoma

  • Han, Xinguang (Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital, Zhengzhou University) ;
  • Han, Yongfu (Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital, Zhengzhou University) ;
  • Jiao, Huifeng (Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital, Zhengzhou University) ;
  • Jie, Yaqiong (School of Stomatology Zhengzhou University)
  • Received : 2014.04.24
  • Accepted : 2014.11.07
  • Published : 2015.02.28
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Abstract

Ectopic expression of $14-3-3{\zeta}$ has been found in various malignancies, including lung cancer, liver cancer, head and neck squamous cell carcinoma (HNSCC), and so on. However, the effect of $14-3-3{\zeta}$ in the regulation of interactions between tumor cells and the immune system has not been previously reported. In this study, we aimed to investigate whether and how $14-3-3{\zeta}$ is implicated in tumor inflammation modulation and immune recognition evasion. In oral squamous cell carcinoma (OSCC) cell lines and cancer tissues, we found that $14-3-3{\zeta}$ is overexpressed. In OSCC cells, $14-3-3{\zeta}$ knockdown resulted in the up-regulated expression of inflammatory cytokines. In contrast, $14-3-3{\zeta}$ introduction attenuated cytokine expression in human normal keratinocytes and fibroblasts stimulated with interferon-${\gamma}$ (IFN-${\gamma}$) and lipopolysaccharide (LPS). Furthermore, supernatants from $14-3-3{\zeta}$ knockdown OSCC cells dramatically altered the response of peritoneal macrophages, dendritic cells and tumor-specific T cells. Interestingly, Stat3 was found to directly interact with $14-3-3{\zeta}$ and its disruption relieved the inhibition induced by $14-3-3{\zeta}$ in tumor inflammation. Taken together, our studies provide evidence that $14-3-3{\zeta}$ may regulate tumor inflammation and immune response through Stat3 signaling in OSCC.

Keywords

References

  1. Aitken, A. (1996). 14-3-3 and its possible role in co-ordinating multiple signalling pathways. Trends Cell Biol. 6, 341-347. https://doi.org/10.1016/0962-8924(96)10029-5
  2. Bettendorf, O., Piffko, J., and Bankfalvi, A. (2004). Prognostic and predictive factors in oral squamous cell cancer: important tools for planning individual therapy? Oral Oncol. 40, 110-119. https://doi.org/10.1016/j.oraloncology.2003.08.010
  3. Bromberg, J.F., Wrzeszczynska, M.H., Devgan, G., Zhao, Y., Pestell, R.G., Albanese, C., and Darnell, J.E., Jr. (1999). Stat3 as an oncogene. Cell 98, 295-303. https://doi.org/10.1016/S0092-8674(00)81959-5
  4. Butt, A.Q., Ahmed, S., Maratha, A., and Miggin, S.M. (2012). 14-3- 3epsilon and 14-3-3sigma inhibit Toll-like receptor (TLR)-mediated proinflammatory cytokine induction. J. Biol. Chem. 287, 38665-38679. https://doi.org/10.1074/jbc.M112.367490
  5. Choi, J.E., Hur, W., Jung, C.K., Piao, L.S., Lyoo, K., Hong, S.W., Kim, S.W., Yoon, H.Y., and Yoon, S.K. (2011). Silencing of 14- 3-3zeta over-expression in hepatocellular carcinoma inhibits tumor growth and enhances chemosensitivity to cis-diammined dichloridoplatium. Cancer Lett. 303, 99-107. https://doi.org/10.1016/j.canlet.2011.01.015
  6. Danes, C.G., Wyszomierski, S.L., Lu, J., Neal, C.L., Yang, W., and Yu, D. (2008). 14-3-3 zeta down-regulates p53 in mammary epithelial cells and confers luminal filling. Cancer Res. 68, 1760-1767. https://doi.org/10.1158/0008-5472.CAN-07-3177
  7. Dhillon, A.S., Yip, Y.Y., Grindlay, G.J., Pakay, J.L., Dangers, M., Hillmann, M., Clark, W., Pitt, A., Mischak, H., and Kolch, W. (2009). The C-terminus of Raf-1 acts as a 14-3-3-dependent activation switch. Cell. Signal. 21, 1645-1651. https://doi.org/10.1016/j.cellsig.2009.07.001
  8. Faisal, A., Saurin, A., Gregory, B., Foxwell, B., and Parker, P.J. (2008). The scaffold MyD88 acts to couple protein kinase Cepsilon to Toll-like receptors. J. Biol. Chem. 283, 18591-18600. https://doi.org/10.1074/jbc.M710330200
  9. Fanger, G.R., Widmann, C., Porter, A.C., Sather, S., Johnson, G.L., and Vaillancourt, R.R. (1998). 14-3-3 proteins interact with specific MEK kinases. J. Biol. Chem. 273, 3476-3483. https://doi.org/10.1074/jbc.273.6.3476
  10. Hashiguchi, M., Sobue, K., and Paudel, H.K. (2000). 14-3-3zeta is an effector of tau protein phosphorylation. J. Biol. Chem. 275, 25247-25254. https://doi.org/10.1074/jbc.M003738200
  11. He, T.C., Zhou, S., da Costa, L.T., Yu, J., Kinzler, K.W., and Vogelstein, B. (1998). A simplified system for generating recombinant adenoviruses. Proc. Natl. Acad. Sci. USA 95, 2509-2514. https://doi.org/10.1073/pnas.95.5.2509
  12. Ichimura, T., Isobe, T., Okuyama, T., Takahashi, N., Araki, K., Kuwano, R., and Takahashi, Y. (1988). Molecular cloning of cDNA coding for brain-specific 14-3-3 protein, a protein kinasedependent activator of tyrosine and tryptophan hydroxylases. Proc. Natl. Acad. Sci. USA 85, 7084-7088. https://doi.org/10.1073/pnas.85.19.7084
  13. Jang, J.S., Cho, H.Y., Lee, Y.J., Ha, W.S., and Kim, H.W. (2004). The differential proteome profile of stomach cancer: identification of the biomarker candidates. Oncol. Res. 14, 491-499. https://doi.org/10.3727/0965040042380441
  14. Jemal, A., Bray, F., Center, M.M., Ferlay, J., Ward, E., and Forman, D. (2011). Global cancer statistics. CA Cancer J. Clin. 61, 69-90. https://doi.org/10.3322/caac.20107
  15. Kwak, B., Mulhaupt, F., Myit, S., and Mach, F. (2000). Statins as a newly recognized type of immunomodulator. Nat Med. 6, 1399-1402. https://doi.org/10.1038/82219
  16. Lakshmi Narendra, B., Eshvendar Reddy, K., Shantikumar, S., and Ramakrishna, S. (2013). Immune system: a double-edged sword in cancer. Inflamm. Res. 62, 823-834. https://doi.org/10.1007/s00011-013-0645-9
  17. Leeman, R.J., Lui, V.W., and Grandis, J.R. (2006). STAT3 as a therapeutic target in head and neck cancer. Expert Opin. Biol. Ther. 6, 231-241. https://doi.org/10.1517/14712598.6.3.231
  18. Levy, D.E., and Darnell, J.E., Jr. (2002). Stats: transcriptional control and biological impact. Nat. Rev. Mol. Cell Biol. 3, 651-662. https://doi.org/10.1038/nrm909
  19. Li, Z., Zhao, J., Du, Y., Park, H.R., Sun, S.Y., Bernal-Mizrachi, L., Aitken, A., Khuri, F.R., and Fu, H. (2008). Down-regulation of 14-3-3zeta suppresses anchorage-independent growth of lung cancer cells through anoikis activation. Proc. Natl. Acad. Sci. USA 105, 162-167. https://doi.org/10.1073/pnas.0710905105
  20. Lin, M., Morrison, C.D., Jones, S., Mohamed, N., Bacher, J., and Plass, C. (2009). Copy number gain and oncogenic activity of YWHAZ/14-3-3zeta in head and neck squamous cell carcinoma. Int. J. Cancer 125, 603-611. https://doi.org/10.1002/ijc.24346
  21. Matta, A., Bahadur, S., Duggal, R., Gupta, S.D., and Ralhan, R. (2007). Over-expression of 14-3-3zeta is an early event in oral cancer. BMC Cancer 7, 169. https://doi.org/10.1186/1471-2407-7-169
  22. Min, B.M., Lee, G., Kim, S.H., Nam, Y.S., Lee, T.S., and Park, W.H. (2004). Electrospinning of silk fibroin nanofibers and its effect on the adhesion and spreading of normal human keratinocytes and fibroblasts in vitro. Biomaterials 25, 1289-1297. https://doi.org/10.1016/j.biomaterials.2003.08.045
  23. Neal, C.L., and Yu, D. (2010). 14-3-3zeta as a prognostic marker and therapeutic target for cancer. Expert Opin. Ther. Targets 14, 1343-1354. https://doi.org/10.1517/14728222.2010.531011
  24. Neal, C.L., Yao, J., Yang, W., Zhou, X., Nguyen, N.T., Lu, J., Danes, C.G., Guo, H., Lan, K.H., Ensor, J., et al. (2009). 14-3-3zeta overexpression defines high risk for breast cancer recurrence and promotes cancer cell survival. Cancer Res. 69, 3425-3432. https://doi.org/10.1158/0008-5472.CAN-08-2765
  25. Neal, C.L., Xu, J., Li, P., Mori, S., Yang, J., Neal, N.N., Zhou, X., Wyszomierski, S.L., and Yu, D. (2012). Overexpression of 14-3- 3zeta in cancer cells activates PI3K via binding the p85 regulatory subunit. Oncogene 31, 897-906. https://doi.org/10.1038/onc.2011.284
  26. O'Shea, J.J., Holland, S.M., and Staudt, L.M. (2013). JAKs and STATs in immunity, immunodeficiency, and cancer. N. Engl. J. Med. 368, 161-170. https://doi.org/10.1056/NEJMra1202117
  27. Ochsenbein, A.F., Sierro, S., Odermatt, B., Pericin, M., Karrer, U., Hermans, J., Hemmi, S., Hengartner, H., and Zinkernagel, R.M. (2001). Roles of tumour localization, second signals and cross priming in cytotoxic T-cell induction. Nature 411, 1058-1064. https://doi.org/10.1038/35082583
  28. Parkin, D.M., Pisani, P., and Ferlay, J. (1999). Estimates of the worldwide incidence of 25 major cancers in 1990. Int. J. Cancer 80, 827-841. https://doi.org/10.1002/(SICI)1097-0215(19990315)80:6<827::AID-IJC6>3.0.CO;2-P
  29. Reuther, G.W., and Pendergast, A.M. (1996). The roles of 14-3-3 proteins in signal transduction. Vitam. Horm. 52, 149-175. https://doi.org/10.1016/S0083-6729(08)60410-0
  30. Saurin, A.T., Durgan, J., Cameron, A.J., Faisal, A., Marber, M.S., and Parker, P.J. (2008). The regulated assembly of a PKCepsilon complex controls the completion of cytokinesis. Nat. Cell Biol. 10, 891-901. https://doi.org/10.1038/ncb1749
  31. Schuster, T.B., Costina, V., Findeisen, P., Neumaier, M., and Ahmad- Nejad, P. (2011). Identification and functional characterization of 14-3-3 in TLR2 signaling. J. Proteome Res. 10, 4661-4670. https://doi.org/10.1021/pr200461p
  32. Silver, D.L., Naora, H., Liu, J., Cheng, W., and Montell, D.J. (2004). Activated signal transducer and activator of transcription (STAT) 3: localization in focal adhesions and function in ovarian cancer cell motility. Cancer Res. 64, 3550-3558. https://doi.org/10.1158/0008-5472.CAN-03-3959
  33. Sriuranpong, V., Park, J.I., Amornphimoltham, P., Patel, V., Nelkin, B.D., and Gutkind, J.S. (2003). Epidermal growth factor receptorindependent constitutive activation of STAT3 in head and neck squamous cell carcinoma is mediated by the autocrine/paracrine stimulation of the interleukin 6/gp130 cytokine system. Cancer Res. 63, 2948-2956.
  34. Sun, L., Stoecklin, G., Van Way, S., Hinkovska-Galcheva, V., Guo, R.F., Anderson, P., and Shanley, T.P. (2007). Tristetraprolin (TTP)-14-3-3 complex formation protects TTP from dephosphorylation by protein phosphatase 2a and stabilizes tumor necrosis factor-alpha mRNA. J. Biol. Chem. 282, 3766-3777.
  35. Wang, T., Niu, G., Kortylewski, M., Burdelya, L., Shain, K., Zhang, S., Bhattacharya, R., Gabrilovich, D., Heller, R., Coppola, D., et al. (2004). Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells. Nat. Med. 10, 48-54. https://doi.org/10.1038/nm976
  36. Wang, M.L., Shin, M.E., Knight, P.A., Artis, D., Silberg, D.G., Suh, E., and Wu, G.D. (2005). Regulation of RELM/FIZZ isoform expression by Cdx2 in response to innate and adaptive immune stimulation in the intestine. Am. J. Physiol. Gastrointest Liver Physiol. 288, G1074-1083. https://doi.org/10.1152/ajpgi.00442.2004
  37. Wang, B., Liu, K., Lin, H.Y., Bellam, N., Ling, S., and Lin, W.C. (2010). 14-3-3Tau regulates ubiquitin-independent proteasomal degradation of p21, a novel mechanism of p21 downregulation in breast cancer. Mol. Cell. Biol. 30, 1508-1527. https://doi.org/10.1128/MCB.01335-09
  38. Wang, X., Crowe, P.J., Goldstein, D., and Yang, J.L. (2012). STAT3 inhibition, a novel approach to enhancing targeted therapy in human cancers (review). Int. J. Oncol. 41, 1181-1191. https://doi.org/10.3892/ijo.2012.1568
  39. Wei, D., Le, X., Zheng, L., Wang, L., Frey, J.A., Gao, A.C., Peng, Z., Huang, S., Xiong, H.Q., Abbruzzese, J.L., et al. (2003). Stat3 activation regulates the expression of vascular endothelial growth factor and human pancreatic cancer angiogenesis and metastasis. Oncogene 22, 319-329. https://doi.org/10.1038/sj.onc.1206122
  40. Yaffe, M.B., Rittinger, K., Volinia, S., Caron, P.R., Aitken, A., Leffers, H., Gamblin, S.J., Smerdon, S.J., and Cantley, L.C. (1997). The structural basis for 14-3-3:phosphopeptide binding specificity. Cell 91, 961-971. https://doi.org/10.1016/S0092-8674(00)80487-0
  41. Yang, X., Cao, W., Zhang, L., Zhang, W., Zhang, X., and Lin, H. (2012). Targeting 14-3-3zeta in cancer therapy. Cancer Gene Ther. 19, 153-159. https://doi.org/10.1038/cgt.2011.85
  42. Yu, H., Kortylewski, M., and Pardoll, D. (2007). Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat. Rev. Immunol. 7, 41-51. https://doi.org/10.1038/nri1995
  43. Zhang, J., Chen, F., Li, W., Xiong, Q., Yang, M., Zheng, P., Li, C., Pei, J., and Ge, F. (2012). 14-3-3zeta interacts with stat3 and regulates its constitutive activation in multiple myeloma cells. PLoS One 7, e29554. https://doi.org/10.1371/journal.pone.0029554

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