Please use this identifier to cite or link to this item:
標題: The role of 14-3-3 zeta protein (YWHAZ) in regulating epithelial plasticity and lung adenocarcinoma cell metastasis
14-3-3 zeta (YWHAZ)蛋白對於肺腺癌細胞 調控上皮塑性與轉移的重要性
作者: 楊孟芳
Fang, Yang-Meng
關鍵字: 14-3-3 zeta protein;14-3-3zeta;lung adenocarcinoma;肺癌;轉移
出版社: 生物醫學研究所
引用: Adamson, P., S. Etienne, P.O. Couraud, V. Calder, and J. Greenwood. 1999. Lymphocyte migration through brain endothelial cell monolayers involves signaling through endothelial ICAM-1 via a rho-dependent pathway. J Immunol. 162:2964-73. Albelda, S.M. 1993. Role of integrins and other cell adhesion molecules in tumor progression and metastasis. Lab Invest. 68:4-17. Albertson, D.G., C. Collins, F. McCormick, and J.W. Gray. 2003. Chromosome aberrations in solid tumors. Nat Genet. 34:369-76. Amit, S., A. Hatzubai, Y. Birman, J.S. Andersen, E. Ben-Shushan, M. Mann, Y. Ben-Neriah, and I. Alkalay. 2002. Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway. Genes Dev. 16:1066-76. Asch, H.L., J.S. Winston, S.B. Edge, P.C. Stomper, and B.B. Asch. 1999. Down-regulation of gelsolin expression in human breast ductal carcinoma in situ with and without invasion. Breast Cancer Res Treat. 55:179-88. Azuma, T., W. Witke, T.P. Stossel, J.H. Hartwig, and D.J. Kwiatkowski. 1998. Gelsolin is a downstream effector of rac for fibroblast motility. Embo J. 17:1362-70. Behrens, J., J.P. von Kries, M. Kuhl, L. Bruhn, D. Wedlich, R. Grosschedl, and W. Birchmeier. 1996. Functional interaction of beta-catenin with the transcription factor LEF-1. Nature. 382:638-42. Birkenfeld, J., H. Betz, and D. Roth. 2003. Identification of cofilin and LIM-domain-containing protein kinase 1 as novel interaction partners of 14-3-3 zeta. Biochem J. 369:45-54. Boutros, M., and M. Mlodzik. 1999. Dishevelled: at the crossroads of divergent intracellular signaling pathways. Mech Dev. 83:27-37. Braga, V.M., M. Betson, X. Li, and N. Lamarche-Vane. 2000. Activation of the small GTPase Rac is sufficient to disrupt cadherin-dependent cell-cell adhesion in normal human keratinocytes. Mol Biol Cell. 11:3703-21. Brent, R. 2000. Genomic biology. Cell. 100:169-83. Bridges, D., and G.B. Moorhead. 2004. 14-3-3 proteins: a number of functions for a numbered protein. Sci STKE. 2004:re10. Bubb, M.R. 2003. Thymosin beta 4 interactions. Vitam Horm. 66:297-316. Cadigan, K.M., and R. Nusse. 1997. Wnt signaling: a common theme in animal development. Genes Dev. 11:3286-305. Chen, J.J., K. Peck, T.M. Hong, S.C. Yang, Y.P. Sher, J.Y. Shih, R. Wu, J.L. Cheng, S.R. Roffler, C.W. Wu, and P.C. Yang. 2001. Global analysis of gene expression in invasion by a lung cancer model. Cancer Res. 61:5223-30. Cooper, J.A., and D.A. Schafer. 2000. Control of actin assembly and disassembly at filament ends. Curr Opin Cell Biol. 12:97-103. Cowin, P., T.M. Rowlands, and S.J. Hatsell. 2005. Cadherins and catenins in breast cancer. Curr Opin Cell Biol. 17:499-508. Datta, S.R., A. Katsov, L. Hu, A. Petros, S.W. Fesik, M.B. Yaffe, and M.E. Greenberg. 2000. 14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation. Mol Cell. 6:41-51. De Corte, V., E. Bruyneel, C. Boucherie, M. Mareel, J. Vandekerckhove, and J. Gettemans. 2002. Gelsolin-induced epithelial cell invasion is dependent on Ras-Rac signaling. Embo J. 21:6781-90. Fan, T., R. Li, N.W. Todd, Q. Qiu, H.B. Fang, H. Wang, J. Shen, R.Y. Zhao, N.P. Caraway, R.L. Katz, S.A. Stass, and F. Jiang. 2007. Up-regulation of 14-3-3zeta in lung cancer and its implication as prognostic and therapeutic target. Cancer Res. 67:7901-6. Fischer, R.S., and V.M. Fowler. 2003. Tropomodulins: life at the slow end. Trends Cell Biol. 13:593-601. Fodde, R., R. Smits, and H. Clevers. 2001. APC, signal transduction and genetic instability in colorectal cancer. Nat Rev Cancer. 1:55-67. Friedl, P., and K. Wolf. 2003. Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer. 3:362-74. Furukawa, R., and M. Fechheimer. 1997. The structure, function, and assembly of actin filament bundles. Int Rev Cytol. 175:29-90. Gao, Z.H., J.M. Seeling, V. Hill, A. Yochum, and D.M. Virshup. 2002. Casein kinase I phosphorylates and destabilizes the beta-catenin degradation complex. Proc Natl Acad Sci U S A. 99:1182-7. Giancotti, V. 2006. Breast cancer markers. Cancer Lett. 243:145-59. Guilford, P. 1999. E-cadherin downregulation in cancer: fuel on the fire? Mol Med Today. 5:172-7. Guo, W., and F.G. Giancotti. 2004. Integrin signalling during tumour progression. Nat Rev Mol Cell Biol. 5:816-26. Gupta, G.P., and J. Massague. 2006. Cancer metastasis: building a framework. Cell. 127:679-95. Hanahan, D., and R.A. Weinberg. 2000. The hallmarks of cancer. Cell. 100:57-70. Harada, N., Y. Tamai, T. Ishikawa, B. Sauer, K. Takaku, M. Oshima, and M.M. Taketo. 1999. Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene. Embo J. 18:5931-42. Herman, I.M. 1993. Actin isoforms. Curr Opin Cell Biol. 5:48-55. Hoffman, P.C., A.M. Mauer, and E.E. Vokes. 2000. Lung cancer. Lancet. 355:479-85. Hsu, S.C., J. Galceran, and R. Grosschedl. 1998. Modulation of transcriptional regulation by LEF-1 in response to Wnt-1 signaling and association with beta-catenin. Mol Cell Biol. 18:4807-18. Hulsken, J., W. Birchmeier, and J. Behrens. 1994. E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton. J Cell Biol. 127:2061-9. Jang, J.S., H.Y. Cho, Y.J. Lee, W.S. Ha, and H.W. Kim. 2004. The differential proteome profile of stomach cancer: identification of the biomarker candidates. Oncol Res. 14:491-9. Jemal, A., A. Thomas, T. Murray, and M. Thun. 2002. Cancer statistics, 2002. CA Cancer J Clin. 52:23-47. Kallioniemi, A., O.P. Kallioniemi, D. Sudar, D. Rutovitz, J.W. Gray, F. Waldman, and D. Pinkel. 1992. Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science. 258:818-21. Khaitlina, S.Y. 2001. Functional specificity of actin isoforms. Int Rev Cytol. 202:35-98. Kuhl, M., L.C. Sheldahl, M. Park, J.R. Miller, and R.T. Moon. 2000. The Wnt/Ca2+ pathway: a new vertebrate Wnt signaling pathway takes shape. Trends Genet. 16:279-83. Kurup, A., and N.H. Hanna. 2004. Treatment of small cell lung cancer. Crit Rev Oncol Hematol. 52:117-26. Larue, L., and A. Bellacosa. 2005. Epithelial-mesenchymal transition in development and cancer: role of phosphatidylinositol 3'' kinase/AKT pathways. Oncogene. 24:7443-54. Leptin, M., and B. Grunewald. 1990. Cell shape changes during gastrulation in Drosophila. Development. 110:73-84. Liu, C., Y. Li, M. Semenov, C. Han, G.H. Baeg, Y. Tan, Z. Zhang, X. Lin, and X. He. 2002. Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell. 108:837-47. Marikawa, Y., and R.P. Elinson. 1998. beta-TrCP is a negative regulator of Wnt/beta-catenin signaling pathway and dorsal axis formation in Xenopus embryos. Mech Dev. 77:75-80. Martinez-Estrada, O.M., A. Culleres, F.X. Soriano, H. Peinado, V. Bolos, F.O. Martinez, M. Reina, A. Cano, M. Fabre, and S. Vilaro. 2006. The transcription factors Slug and Snail act as repressors of Claudin-1 expression in epithelial cells. Biochem J. 394:449-57. Matsumoto, Y., K. Tanaka, K. Harimaya, F. Nakatani, S. Matsuda, and Y. Iwamoto. 2001. Small GTP-binding protein, Rho, both increased and decreased cellular motility, activation of matrix metalloproteinase 2 and invasion of human osteosarcoma cells. Jpn J Cancer Res. 92:429-38. Matta, A., S. Bahadur, R. Duggal, S.D. Gupta, and R. Ralhan. 2007. Over-expression of 14-3-3zeta is an early event in oral cancer. BMC Cancer. 7:169. Meyer, T., and I.R. Hart. 1998. Mechanisms of tumour metastasis. Eur J Cancer. 34:214-21. Miller, J.R., A.M. Hocking, J.D. Brown, and R.T. Moon. 1999. Mechanism and function of signal transduction by the Wnt/beta-catenin and Wnt/Ca2+ pathways. Oncogene. 18:7860-72. Mitchison, T.J., and L.P. Cramer. 1996. Actin-based cell motility and cell locomotion. Cell. 84:371-9. Nicholson-Dykstra, S., H.N. Higgs, and E.S. Harris. 2005. Actin dynamics: growth from dendritic branches. Curr Biol. 15:R346-57. Niemantsverdriet, M., K. Wagner, M. Visser, and C. Backendorf. 2008. Cellular functions of 14-3-3 zeta in apoptosis and cell adhesion emphasize its oncogenic character. Oncogene. 27:1315-9. Niklinski, J., W. Niklinska, J. Laudanski, E. Chyczewska, and L. Chyczewski. 2001. Prognostic molecular markers in non-small cell lung cancer. Lung Cancer. 34 Suppl 2:S53-8. Oksvold, M.P., H.S. Huitfeldt, and W.Y. Langdon. 2004. Identification of 14-3-3zeta as an EGF receptor interacting protein. FEBS Lett. 569:207-10. Osiak, A.E., G. Zenner, and S. Linder. 2005. Subconfluent endothelial cells form podosomes downstream of cytokine and RhoGTPase signaling. Exp Cell Res. 307:342-53. Peng, B.H., J.C. Lee, and G.A. Campbell. 2003. In vitro protein complex formation with cytoskeleton-anchoring domain of occludin identified by limited proteolysis. J Biol Chem. 278:49644-51. Polakis, P. 2000. Wnt signaling and cancer. Genes Dev. 14:1837-51. Robertson, S.P. 2005. Filamin A: phenotypic diversity. Curr Opin Genet Dev. 15:301-7. Sahai, E., and C.J. Marshall. 2002. ROCK and Dia have opposing effects on adherens junctions downstream of Rho. Nat Cell Biol. 4:408-15. Sheldahl, L.C., M. Park, C.C. Malbon, and R.T. Moon. 1999. Protein kinase C is differentially stimulated by Wnt and Frizzled homologs in a G-protein-dependent manner. Curr Biol. 9:695-8. Silacci, P., L. Mazzolai, C. Gauci, N. Stergiopulos, H.L. Yin, and D. Hayoz. 2004. Gelsolin superfamily proteins: key regulators of cellular functions. Cell Mol Life Sci. 61:2614-23. Small, J.V., K. Anderson, and K. Rottner. 1996. Actin and the coordination of protrusion, attachment and retraction in cell crawling. Biosci Rep. 16:351-68. Soo, K., M.P. O''Rourke, P.L. Khoo, K.A. Steiner, N. Wong, R.R. Behringer, and P.P. Tam. 2002. Twist function is required for the morphogenesis of the cephalic neural tube and the differentiation of the cranial neural crest cells in the mouse embryo. Dev Biol. 247:251-70. Sreenath, T., L.M. Matrisian, W. Stetler-Stevenson, S. Gattoni-Celli, and R.O. Pozzatti. 1992. Expression of matrix metalloproteinase genes in transformed rat cell lines of high and low metastatic potential. Cancer Res. 52:4942-7. Staal, F.J., M. Noort Mv, G.J. Strous, and H.C. Clevers. 2002. Wnt signals are transmitted through N-terminally dephosphorylated beta-catenin. EMBO Rep. 3:63-8. Steeg, P.S. 2003. Metastasis suppressors alter the signal transduction of cancer cells. Nat Rev Cancer. 3:55-63. Stomski, F.C., M. Dottore, W. Winnall, M.A. Guthridge, J. Woodcock, C.J. Bagley, D.T. Thomas, R.K. Andrews, M.C. Berndt, and A.F. Lopez. 1999. Identification of a 14-3-3 binding sequence in the common beta chain of the granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 receptors that is serine-phosphorylated by GM-CSF. Blood. 94:1933-42. Sun, H.Q., K. Kwiatkowska, and H.L. Yin. 1995. Actin monomer binding proteins. Curr Opin Cell Biol. 7:102-10. Takai, Y., T. Sasaki, and T. Matozaki. 2001. Small GTP-binding proteins. Physiol Rev. 81:153-208. Tian, Q., X.C. He, L. Hood, and L. Li. 2005. Bridging the BMP and Wnt pathways by PI3 kinase/Akt and 14-3-3zeta. Cell Cycle. 4:215-6. Van Der Hoeven, P.C., J.C. Van Der Wal, P. Ruurs, and W.J. Van Blitterswijk. 2000. Protein kinase C activation by acidic proteins including 14-3-3. Biochem J. 347 Pt 3:781-5. van Golen, K.L., Z.F. Wu, X.T. Qiao, L. Bao, and S.D. Merajver. 2000. RhoC GTPase overexpression modulates induction of angiogenic factors in breast cells. Neoplasia. 2:418-25. van Noort, M., M. van de Wetering, and H. Clevers. 2002. Identification of two novel regulated serines in the N terminus of beta-catenin. Exp Cell Res. 276:264-72. Vandekerckhove, J., and K. Weber. 1978. Mammalian cytoplasmic actins are the products of at least two genes and differ in primary structure in at least 25 identified positions from skeletal muscle actins. Proc Natl Acad Sci U S A. 75:1106-10. Vleminckx, K., L. Vakaet, Jr., M. Mareel, W. Fiers, and F. van Roy. 1991. Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell. 66:107-19. Welch, M.D. 1999. The world according to Arp: regulation of actin nucleation by the Arp2/3 complex. Trends Cell Biol. 9:423-7. Wodarz, A., and R. Nusse. 1998. Mechanisms of Wnt signaling in development. Annu Rev Cell Dev Biol. 14:59-88. Woodhouse, E.C., R.F. Chuaqui, and L.A. Liotta. 1997. General mechanisms of metastasis. Cancer. 80:1529-37. Worthylake, R.A., S. Lemoine, J.M. Watson, and K. Burridge. 2001. RhoA is required for monocyte tail retraction during transendothelial migration. J Cell Biol. 154:147-60. Yaffe, M.B., K. Rittinger, S. Volinia, P.R. Caron, A. Aitken, H. Leffers, S.J. Gamblin, S.J. Smerdon, and L.C. Cantley. 1997. The structural basis for 14-3-3:phosphopeptide binding specificity. Cell. 91:961-71. Yamamoto, K., M. Seto, S. Iida, H. Komatsu, N. Kamada, S. Kojima, Y. Kodera, S. Nakazawa, H. Saito, T. Takahashi, and et al. 1994. A reverse transcriptase-polymerase chain reaction detects heterogeneous chimeric mRNAs in leukemias with 11q23 abnormalities. Blood. 83:2912-21. Yang, J., S.A. Mani, J.L. Donaher, S. Ramaswamy, R.A. Itzykson, C. Come, P. Savagner, I. Gitelman, A. Richardson, and R.A. Weinberg. 2004. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 117:927-39. Zang, L., D. Palmer Toy, W.S. Hancock, D.C. Sgroi, and B.L. Karger. 2004. Proteomic analysis of ductal carcinoma of the breast using laser capture microdissection, LC-MS, and 16O/18O isotopic labeling. J Proteome Res. 3:604-12. Zhuge, Y., and J. Xu. 2001. Rac1 mediates type I collagen-dependent MMP-2 activation. role in cell invasion across collagen barrier. J Biol Chem. 276:16248-56.
Lung cancer, predominantly non-small-cell lung cancer (NSCLC), is the most common cause of cancer deaths worldwide, and metastasis is the major cause leading to mortality for cancer patients. The alteration of epithelial plasticity is crucial events during metastasis. To identify the novel metastasis-related genes, we used a method that simultaneously integrated microarray-based comparative genomic hybridization and affymetrix gene expression profiles to identifiy a potential candidate, 14-3-3zeta, in a lung cancer cell line model with different invasion capability (CL1-5 > CL1-0 cell line). 14-3-3zeta protein plays an important role in a wide variety of cellular processes, including signal transduction, cell cycle regulation and apoptosis. However, its role in lung cancer metastasis is unclear. This study will investigate the role of 14-3-3zeta protein in regulating epithelial plasticity and metastasis of lung adenocarcinoma cell. First, microarray data will be confirmed by real-time PCR and western blotting to demonstrate that the genomic copy number, mRNA and protein level of 14-3-3zeta in CL1-5 and CL1-0 lung caner cells. We also observe the distribution of 14-3-3zeta protein in subcellular localization. Second, we will overexpress or silence 14-3-3zeta in lung caner cells and estimate the ability of invasion, migration, as well as morphology. According to preliminary results, we presume that the protein may be involved in tumor metastasis via cytoskeleton rearrangement and regulating epithelial plasticity. To evaluate the alternation of epithelial plasticity, the amount of EMT marker,and G/F actin ratio will be performed by western blotting and immunofluorescence. In addition, we clarify the interaction molecule and modulating pathway of 14-3-3zeta protein. Furthermore, stable lung adenocarcinoma cell lines will be seeded onto immune-compromised (SCID) mice to suggest the influence of 14-3-3zeta protein. Consistent with an animal experiment, 14-3-3zeta is indeed essential for tumorigenesis and lung tumor metastasis. Finally, we check 14-3-3zeta expression in lung adenocarcinoma specimen with different stage, and analyze the survival and recurrent of 60 patients. These efforts may assist us to understand the role of 14-3-3zeta protein in human lung adenocarcinoma metastasis, and may offer some help in the treatment of lung cancer.

肺癌,尤其是肺腺癌,是近年來具有高發生率和極高死亡率之惡性腫瘤,而癌轉移則是導致病患死亡的主因。癌轉移與細胞上皮塑性(epithelial plasticity)的改變有很大的關連。為找尋新的癌轉移相關基因,我們以競爭性基因體核酸雜交微陣列(CGHarray)分析不同侵襲與轉移能力肺癌細胞株之基因體中基因拷貝數的變異(CL1-0
其他識別: U0005-2508200817144400
Appears in Collections:生物醫學研究所

Show full item record

Google ScholarTM


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.