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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Macrophage inhibitory cytokine-1 transactivates ErbB family receptors via the activation of Src in SK-BR-3 human breast cancer cells

  • Park, Yun-Jung (Departments of Biochemistry, College of Natural Sciences, Kangwon National University) ;
  • Lee, Han-Soo (Departments of Biology, College of Natural Sciences, Kangwon National University) ;
  • Lee, Jeong-Hyung (Departments of Biochemistry, College of Natural Sciences, Kangwon National University)
  • Published : 2010.02.28
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Abstract

The function of macrophage inhibitory cytokine-1 (MIC-1) in cancer remains controversial, and its signaling pathways remain poorly understood. In this study, we demonstrate that MIC-1 induces the transactivation of EGFR, ErbB2, and ErbB3 through the activation of c-Src in SK-BR-3 breast cells. MIC-1 induced significant phosphorylation of EGFR at Tyr845, ErbB2 at Tyr877, and ErbB3 at Tyr1289 as well as Akt and p38, Erk1/2, and JNK mitogen-activated protein kinases (MAPKs). Treatment of SK-BR-3 cells with MIC-1 increased the phosphorylation level of Src at Tyr416, and induced invasiveness of those cells. Inhibition of c-Src activity resulted in the complete abolition of MIC-1-induced phosphorylation of the EGFR, ErbB2, and ErbB3, as well as invasiveness and matrix metalloproteinase (MMP)-9 expression in SK-BR-3 cells. Collectively, these results show that MIC-1 may participate in the malignant progression of certain cancer cells through the activation of c-Src, which in turn may transactivate ErbB-family receptors.

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References

  1. Strelau, J., Bottner, M., Lingor, P., Suter-Crazzolara, C., Galter, D., Jaszai, J., Sullivan, A., Schober, A., Krieglstein, K. and Unsicker, K. (2000) GDF-15/MIC-1 a novel member of the TGF-$\beta$ superfamily. J. Neural. Transm. Suppl. 60, 273-276
  2. Bootcov, M. R., Bauskin, A. R., Valenzuela, S. M., Moore, A. G., Bansal, M., He, X. Y., Zhang, H. P., Donnellan, M., Mahler, S., Pryor, K., Walsh, B. J., Nicholson, R. C., Fairlie, W. D., Por, S. B., Robbins, J. M. and Breit, S. N. (1997) MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-$\beta$ superfamily. Proc. Natl. Acad. Sci. U.S.A. 94, 11514-11519 https://doi.org/10.1073/pnas.94.21.11514
  3. Bauskin, A. R., Brown, D. A., Kuffner, T., Johnen, H., Luo, X. W., Hunter, M. and Breit, S. N. (2006) Role of macrophage inhibitory cytokine-1 in tumorigenesis and diagnosis of cancer. Cancer Res. 66, 4983-4986 https://doi.org/10.1158/0008-5472.CAN-05-4067
  4. Paralkar, V. M., Vail, A. L., Grasser, W. A., Brown, T. A., Xu, H., Vukicevic, S., Ke, H. Z., Qi, H., Owen, T. A. and Thompson, D. D. (1998) Cloning and characterization of a novel member of the transforming growth factor-$\beta$/bone morphogenetic protein family. J. Biol. Chem. 273, 13760- 13767 https://doi.org/10.1074/jbc.273.22.13760
  5. Hromas, R., Hufford, M., Sutton, J., Xu, D., Li, Y. and Lu, L. (1997) PLAB, a novel placental bone morphogenetic protein. Biochim. Biophys. Acta. 1354, 40-44 https://doi.org/10.1016/S0167-4781(97)00122-X
  6. Kempf, T., Eden, M., Strelau, J., Naguib, M., Willenbockel, C., Tongers, J., Heineke, J., Kotlarz, D., Xu, J., Molkentin, J. D., Niessen, H. W., Drexler, H. and Wollert, K. C. (2006) The transforming growth factor-$\beta$ superfamily member growth-differentiation factor-15 protects the heart from ischemia/reperfusion injury. Circ. Res. 98, 351-360 https://doi.org/10.1161/01.RES.0000202805.73038.48
  7. Welsh, J. B., Sapinoso, L. M., Su, A. I., Kern, S. G., Wang-Rodriguez, J., Moskaluk, C. A., Frierson, H. F. Jr. and Hampton, G. M. (2001) Analysis of gene expression identifies candidate markers and pharmacological targets in prostate cancer. Cancer Res. 61, 5974-5978
  8. Buckhaults, P., Rago, C., St. Croix, B., Romans, K. E., Saha, S., Zhang, L., Vogelstein, B. and Kinzler, K. W. (2001) Secreted and cell surface genes expressed in benign and malignant colorectal tumors. Cancer Res. 61, 6996-7001
  9. Welsh, J. B., Sapinoso, L. M., Kern, S. G., Brown, D. A., Liu, T., Bauskin, A. R., Ward, R. L., Hawkins, N. J., Quinn, D. I., Russell, P. J., Sutherland, R. L., Breit, S. N., Moskaluk, C. A., Frierson, H. F. and Hampton, G. M. (2003) Large-scale delineation of secreted protein biomarkers overexpressed in cancer tissue and serum. Proc. Natl. Acad. Sci. U.S.A. 100, 3410-3415 https://doi.org/10.1073/pnas.0530278100
  10. Brown, D. A., Ward, R. L., Buckhaults, P., Liu, T., Romans, K. E., Hawkins, N. J., Bauskin, A. R., Kinzler, K. W., Vogelstein, B. and Breit, S. N. (2003) MIC-1 serum level and genotype: associations with progress and prognosis of colorectal carcinoma. Clin. Cancer Res. 9, 2642- 2650
  11. Koopmann, J., Buckhaults, P., Brown, D. A., Zahurak, M. L., Sato, N., Fukushima, N., Sokoll, L. J., Chan, D. W., Yeo, C. J,, Hruban, R. H., Breit, S. N., Kinzler, K. W., Vogelstein, B. and Goggins, M. (2004) Serum macrophage inhibitory cytokine 1 as a marker of pancreatic and other periampullary cancers. Clin. Cancer Res. 10, 2386-2392 https://doi.org/10.1158/1078-0432.CCR-03-0165
  12. Li, P. X., Wong, J., Ayed, A,. Ngo, D., Brade, A. M., Arrowsmith, C., Austin, R. C. and Klamut, H. J. (2000) Placental transforming growth factor-$\beta$ is a downstream mediator of the growth arrest and apoptotic response of tumor cells to DNA damage and p53 overexpression. J. Biol. Chem. 75, 20127-20135
  13. Tan, M., Wang, Y., Guan, K. and Sun, Y. (2000) PTGF-$\beta$, a type $\beta$ transforming growth factor (TGF-$\beta$) superfamily member, is a p53 target gene that inhibits tumor cell growth via TGF-$\beta$ signaling pathway. Proc. Natl. Acad. Sci. U.S.A. 97, 109-114 https://doi.org/10.1073/pnas.97.1.109
  14. Graichen, R., Liu, D., Sun, Y., Lee, K. O. and Lobie, P. E. (2002) Autocrine human growth hormone inhibits placental transforming growth factor-$\beta$ gene transcription to prevent apoptosis and allow cell cycle progression of human mammary carcinoma cells. J. Biol. Chem. 277, 26662-26672 https://doi.org/10.1074/jbc.M109931200
  15. Albertoni, M., Shaw, P. H., Nozaki, M., Godard, S., Tenan, M., Hamou, M. F., Fairlie, D. W., Breit, S. N., Paralkar, V. M., de Tribolet, N., Van Meir, E. G. and Hegi, M. E. (2002) Anoxia induces macrophage inhibitory cytokine-1 (MIC-1) in glioblastoma cells independently of p53 and HIF-1. Oncogene 21, 4212-4219 https://doi.org/10.1038/sj.onc.1205610
  16. Lee, D. H., Yang, Y., Lee, S. J., Kim, K. Y., Koo, T. H., Shin, S. M., Song, K. S., Lee, Y. H., Kim, Y. J., Lee, J. J., Choi, I. and Lee, J. H. (2003) Macrophage inhibitory cytokine- 1 induces the invasiveness of gastric cancer cells by up-regulating the urokinase-type plasminogen activator system. Cancer Res. 63, 4648-4655
  17. Kim, K. K., Lee, J. J., Yang, Y., You, K. H., and Lee, J. H. (2008) Macrophage inhibitory cytokine-1 activates AKT and ERK-1/2 via the transactivation of ErbB2 in human breast and gastric cancer cells. Carcinogenesis 19, 704-712
  18. Boyle, G. M., Pedley, J., Martyn, A. C., Banducci, K. J., Strutton, G. M, Brown , D. A., Breit, S. N. and Parsons, P. G. (2009) Macrophage inhibitory cytokine-1 is overexpressed in malignant melanoma and is associated with tumorigenicity. J. Invest. Dermatol. 129, 383-391 https://doi.org/10.1038/jid.2008.270
  19. Johnen, H., Lin, S., Kuffner, T., Brown, D. A., Tsai, V. W., Bauskin, A. R., Wu, L., Pankhurst, G., Jiang, L., Junankar, S., Hunter, M., Fairlie, W. D., Lee, N. J., Enriquez, R. F., Baldock, P. A., Corey, E., Apple ,F. S, Murakami, M. M, Lin, E. J., Wang, C., During, M. J., Sainsbury, A., Herzog, H. and Breit, S. N. (2007) Tumor-induced anorexia and weight loss are mediated by the TGF-$\beta$ superfamily cytokine MIC-1. Nat. Med. 13, 1333-1340 https://doi.org/10.1038/nm1677
  20. Olayioye, M. A., Neve, R. M., Lane, H. A. and Hynes, N. E. (2000) The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J. 19, 3159-3167 https://doi.org/10.1093/emboj/19.13.3159
  21. Yarden, Y. and Sliwkowski, M. X. (2001) Untangling the ErbB signalling network. Nat. Rev. Mol. Cell. Biol. 2, 127-137 https://doi.org/10.1038/35052073
  22. Zwick, E., Hackel, P. O., Prenzel, N. and Ullrich, A. (1999) The EGF receptor as central transducer of heterologous signalling systems. Trends Pharmacol. Sci. 20, 408-412 https://doi.org/10.1016/S0165-6147(99)01373-5
  23. Argast, G. M., Campbell, J. S., Brooling, J. T. and Fausto, N. (2004) Epidermal growth factor receptor transactivation mediates tumor necrosis factor-induced hepatocyte replication. J. Biol. Chem. 279, 34530-34536 https://doi.org/10.1074/jbc.M405703200
  24. Qiu, Y., Ravi, L. and Kung, H. J. (1998) Requirement of ErbB2 for signalling by interleukin-6 in prostate carcinoma cells. Nature 393, 83-85 https://doi.org/10.1038/30012
  25. Cabioglu, N., Summy, J., Miller, C., Parikh, N. U., Sahin, A. A., Tuzlali, S., Pumiglia, K., Gallick, G. E., and Price, J. E. (2005) CXCL-12/stromal cell-derived factor-1alpha transactivates HER2-neu in breast cancer cells by a novel pathway involving Src kinase activation. Cancer Res. 65, 6493-6497 https://doi.org/10.1158/0008-5472.CAN-04-1303
  26. Fischer, O. M., Hart, S., Gschwind, A. and Ullrich, A. (2003) EGFR signal transactivation in cancer cells. Biochem. Soc. Trans. 31, 1203-1208 https://doi.org/10.1042/BST0311203
  27. Tice, D. A., Biscardi, J. S., Nickles, A. L., and Parsons, S. J. (1999) Mechanism of biological synergy between cellular Src and epidermal growth factor receptor. Proc. Natl. Acad. Sci. U.S.A. 96, 1415-1420 https://doi.org/10.1073/pnas.96.4.1415
  28. Ishizawar, R. C., Miyake, T. and Parsons, S. J. (2007) c-Src modulates ErbB2 and ErbB3 heterocomplex formation and function. Oncogene 26, 3503-3510 https://doi.org/10.1038/sj.onc.1210138
  29. Xu, W., Yuan, X., Beebe, K., Xiang, Z. and Neckers, L. (2007) Loss of Hsp90 association up-regulates Src-dependent ErbB2 activity. Mol. Cell. Biol. 27, 220-228 https://doi.org/10.1128/MCB.00899-06
  30. Biscardi, J. S., Maa, M. C., Tice, D. A., Cox, M. E., Leu, T. H. and Parsons, S. J. (1999) c-Src-mediated phosphorylation of the epidermal growth factor receptor on Tyr845 and Tyr1101 is associated with modulation of receptor function. J. Biol. Chem. 274, 8335-8343 https://doi.org/10.1074/jbc.274.12.8335
  31. Mook, O. R., Frederiks, W. M. and Van Noorden, C. J. (2004) The role of gelatinases in colorectal cancer progression and metastasis. Biochim. Biophys. Acta. 1705, 69-89
  32. Wu, Z. S., Wu, Q., Yang, J. H., Wang, H. Q., Ding, X. D., Yang, F. and Xu, X. C. (2008) Prognostic significance of MMP-9 and TIMP-1 serum and tissue expression in breast cancer. Int. J. Cancer. 122, 2050-2056 https://doi.org/10.1002/ijc.23337
  33. Kim, S., Choi, J. H., Lim, H. I., Lee, S. K., Kim, W. W., Cho, S., Kim, J. S., Kim, J. H., Choe, J. H., Nam, S. J., Lee, J. E. and Yang, J. H. (2009) EGF-induced MMP-9 expression is mediated by the JAK3/ERK pathway, but not by the JAK3/STAT-3 pathway in a SKBR3 breast cancer cell line. Cell Signal 21, 892-898 https://doi.org/10.1016/j.cellsig.2009.01.034
  34. Yao, J., Xiong, S., Klos, K., Nguyen, N., Grijalva, R., Li, P., and Yu, D. (2001) Multiple signaling pathways involved in activation of matrix metalloproteinase-9 (MMP-9) by heregulin-$\beta$1 in human breast cancer cells. Oncogene 20, 8066-8074 https://doi.org/10.1038/sj.onc.1204944
  35. Cho, H. J. and Nam, K. S. (2007) Inhibitory effect of ginkgolide B on platelet aggregation in a cAMP- and cGMPdependent manner by activated MMP-9. J. Biochem. Mol. Biol. 40, 678-683 https://doi.org/10.5483/BMBRep.2007.40.5.678

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