Please use this identifier to cite or link to this item:
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dc.contributorPan-Chyr Yangen_US
dc.contributorSung-Liang Yuen_US
dc.contributor.advisorJeremy J.W. Chenen_US
dc.contributor.authorChen, Ching-Hsienen_US
dc.identifier.citation1. Nugent, W. C., Edney, M. T., Hammerness, P. G., Dain, B. J., Maurer, L. H., and Rigas, J. R. Non-small cell lung cancer at the extremes of age: impact on diagnosis and treatment. Ann Thorac Surg, 63: 193-197, 1997. 2. Rapp, E., Pater, J. L., Willan, A., Cormier, Y., Murray, N., Evans, W. K., Hodson, D. I., Clark, D. A., Feld, R., Arnold, A. M., and et al. Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer--report of a Canadian multicenter randomized trial. J Clin Oncol, 6: 633-641, 1988. 3. Mountain, C. F. Revisions in the International System for Staging Lung Cancer. Chest, 111: 1710-1717, 1997. 4. Meyer, T. and Hart, I. R. Mechanisms of tumour metastasis. Eur J Cancer, 34: 214-221, 1998. 5. Yoneda, T. Cellular and molecular mechanisms of breast and prostate cancer metastasis to bone. Eur J Cancer, 34: 240-245, 1998. 6. Chen, J. J., Peck, K., Hong, T. M., Yang, S. C., Sher, Y. P., Shih, J. Y., Wu, R., Cheng, J. L., Roffler, S. R., Wu, C. W., and Yang, P. C. Global analysis of gene expression in invasion by a lung cancer model. Cancer Res, 61: 5223-5230, 2001. 7. Ross, D. T., Scherf, U., Eisen, M. B., Perou, C. M., Rees, C., Spellman, P., Iyer, V., Jeffrey, S. S., Van de Rijn, M., Waltham, M., Pergamenschikov, A., Lee, J. C., Lashkari, D., Shalon, D., Myers, T. G., Weinstein, J. N., Botstein, D., and Brown, P. O. Systematic variation in gene expression patterns in human cancer cell lines. Nat Genet, 24: 227-235, 2000. 8. Hong, T. M., Yang, P. C., Peck, K., Chen, J. J., Yang, S. C., Chen, Y. C., and Wu, C. W. Profiling the downstream genes of tumor suppressor PTEN in lung cancer cells by complementary DNA microarray. Am J Respir Cell Mol Biol, 23: 355-363, 2000. 9. Khan, J., Saal, L. H., Bittner, M. L., Chen, Y., Trent, J. M., and Meltzer, P. S. Expression profiling in cancer using cDNA microarrays. Electrophoresis, 20: 223-229, 1999. 10. Iyer, V. R., Eisen, M. B., Ross, D. T., Schuler, G., Moore, T., Lee, J. C., Trent, J. M., Staudt, L. M., Hudson, J., Jr., Boguski, M. S., Lashkari, D., Shalon, D., Botstein, D., and Brown, P. O. The transcriptional program in the response of human fibroblasts to serum. Science, 283: 83-87, 1999. 11. Oksvold, M. P., Huitfeldt, H. S., and Langdon, W. Y. Identification of 14-3-3zeta as an EGF receptor interacting protein. FEBS Lett, 569: 207-210, 2004. 12. Bialkowska, K., Zaffran, Y., Meyer, S. C., and Fox, J. E. 14-3-3 zeta mediates integrin-induced activation of Cdc42 and Rac. Platelet glycoprotein Ib-IX regulates integrin-induced signaling by sequestering 14-3-3 zeta. J Biol Chem, 278: 33342-33350, 2003. 13. Birkenfeld, J., Betz, H., and Roth, D. Identification of cofilin and LIM-domain-containing protein kinase 1 as novel interaction partners of 14-3-3 zeta. Biochem J, 369: 45-54, 2003. 14. Deakin, N. O., Bass, M. D., Warwood, S., Schoelermann, J., Mostafavi-Pour, Z., Knight, D., Ballestrem, C., and Humphries, M. J. An integrin-alpha4-14-3-3zeta-paxillin ternary complex mediates localised Cdc42 activity and accelerates cell migration. J Cell Sci, 122: 1654-1664, 2009. 15. Li, F. Q., Mofunanya, A., Harris, K., and Takemaru, K. Chibby cooperates with 14-3-3 to regulate beta-catenin subcellular distribution and signaling activity. J Cell Biol, 181: 1141-1154, 2008. 16. Danes, C. G., Wyszomierski, S. L., Lu, J., Neal, C. L., Yang, W., and Yu, D. 14-3-3 zeta down-regulates p53 in mammary epithelial cells and confers luminal filling. Cancer Res, 68: 1760-1767, 2008. 17. Fan, T., Li, R., Todd, N. W., Qiu, Q., Fang, H. B., Wang, H., Shen, J., Zhao, R. Y., Caraway, N. P., Katz, R. L., Stass, S. A., and Jiang, F. Up-regulation of 14-3-3zeta in lung cancer and its implication as prognostic and therapeutic target. Cancer Res, 67: 7901-7906, 2007. 18. Lin, M., Morrison, C. D., Jones, S., Mohamed, N., Bacher, J., and Plass, C. Copy number gain and oncogenic activity of YWHAZ/14-3-3zeta in head and neck squamous cell carcinoma. Int J Cancer, 125: 603-611, 2009. 19. Li, Z., Zhao, J., Du, Y., Park, H. R., Sun, S. Y., Bernal-Mizrachi, L., Aitken, A., Khuri, F. R., and Fu, H. Down-regulation of 14-3-3zeta suppresses anchorage-independent growth of lung cancer cells through anoikis activation. Proc Natl Acad Sci U S A, 105: 162-167, 2008. 20. Matta, A., Bahadur, S., Duggal, R., Gupta, S. D., and Ralhan, R. Over-expression of 14-3-3zeta is an early event in oral cancer. BMC Cancer, 7: 169, 2007. 21. Tsai, M. F., Wang, C. C., Chang, G. C., Chen, C. Y., Chen, H. Y., Cheng, C. L., Yang, Y. P., Wu, C. Y., Shih, F. Y., Liu, C. C., Lin, H. P., Jou, Y. S., Lin, S. C., Lin, C. W., Chen, W. J., Chan, W. K., Chen, J. J., and Yang, P. C. A new tumor suppressor DnaJ-like heat shock protein, HLJ1, and survival of patients with non-small-cell lung carcinoma. J Natl Cancer Inst, 98: 825-838, 2006. 22. Wang, C. C., Tsai, M. F., Hong, T. M., Chang, G. C., Chen, C. Y., Yang, W. M., Chen, J. J., and Yang, P. C. The transcriptional factor YY1 upregulates the novel invasion suppressor HLJ1 expression and inhibits cancer cell invasion. Oncogene, 24: 4081-4093, 2005. 23. Chang, T. P., Yu, S. L., Lin, S. Y., Hsiao, Y. J., Chang, G. C., Yang, P. C., and Chen, J. J. Tumor suppressor HLJ1 binds and functionally alters nucleophosmin via activating enhancer binding protein 2alpha complex formation. Cancer Res, 70: 1656-1667. 24. Edwards, B. K., Brown, M. L., Wingo, P. A., Howe, H. L., Ward, E., Ries, L. A., Schrag, D., Jamison, P. M., Jemal, A., Wu, X. C., Friedman, C., Harlan, L., Warren, J., Anderson, R. N., and Pickle, L. W. Annual report to the nation on the status of cancer, 1975-2002, featuring population-based trends in cancer treatment. J Natl Cancer Inst, 97: 1407-1427, 2005. 25. Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., and Thun, M. J. Cancer statistics, 2009. CA Cancer J Clin, 59: 225-249, 2009. 26. Fidler, I. J. The pathogenesis of cancer metastasis: the ''seed and soil'' hypothesis revisited. Nat Rev Cancer, 3: 453-458, 2003. 27. Grunert, S., Jechlinger, M., and Beug, H. Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis. Nat Rev Mol Cell Biol, 4: 657-665, 2003. 28. Bogenrieder, T. and Herlyn, M. Axis of evil: molecular mechanisms of cancer metastasis. Oncogene, 22: 6524-6536, 2003. 29. Gimona, M., Buccione, R., Courtneidge, S. A., and Linder, S. Assembly and biological role of podosomes and invadopodia. Curr Opin Cell Biol, 20: 235-241, 2008. 30. Linder, S. The matrix corroded: podosomes and invadopodia in extracellular matrix degradation. Trends Cell Biol, 17: 107-117, 2007. 31. Poincloux, R., Lizarraga, F., and Chavrier, P. Matrix invasion by tumour cells: a focus on MT1-MMP trafficking to invadopodia. J Cell Sci, 122: 3015-3024, 2009. 32. Linder, S. and Kopp, P. Podosomes at a glance. J Cell Sci, 118: 2079-2082, 2005. 33. Destaing, O., Sanjay, A., Itzstein, C., Horne, W. C., Toomre, D., De Camilli, P., and Baron, R. The tyrosine kinase activity of c-Src regulates actin dynamics and organization of podosomes in osteoclasts. Mol Biol Cell, 19: 394-404, 2008. 34. Oikawa, T., Itoh, T., and Takenawa, T. Sequential signals toward podosome formation in NIH-src cells. J Cell Biol, 182: 157-169, 2008. 35. Thompson, O., Kleino, I., Crimaldi, L., Gimona, M., Saksela, K., and Winder, S. J. Dystroglycan, Tks5 and Src mediated assembly of podosomes in myoblasts. PLoS One, 3: e3638, 2008. 36. Clevers, H. Wnt/beta-catenin signaling in development and disease. Cell, 127: 469-480, 2006. 37. Li, L., Yuan, H., Weaver, C. D., Mao, J., Farr, G. H., 3rd, Sussman, D. J., Jonkers, J., Kimelman, D., and Wu, D. Axin and Frat1 interact with dvl and GSK, bridging Dvl to GSK in Wnt-mediated regulation of LEF-1. Embo J, 18: 4233-4240, 1999. 38. Aberle, H., Bauer, A., Stappert, J., Kispert, A., and Kemler, R. beta-catenin is a target for the ubiquitin-proteasome pathway. Embo J, 16: 3797-3804, 1997. 39. Ben-Ze''ev, A., Shtutman, M., and Zhurinsky, J. The integration of cell adhesion with gene expression: the role of beta-catenin. Exp Cell Res, 261: 75-82, 2000. 40. Conacci-Sorrell, M., Simcha, I., Ben-Yedidia, T., Blechman, J., Savagner, P., and Ben-Ze''ev, A. Autoregulation of E-cadherin expression by cadherin-cadherin interactions: the roles of beta-catenin signaling, Slug, and MAPK. J Cell Biol, 163: 847-857, 2003. 41. Shtutman, M., Zhurinsky, J., Simcha, I., Albanese, C., D''Amico, M., Pestell, R., and Ben-Ze''ev, A. The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proc Natl Acad Sci U S A, 96: 5522-5527, 1999. 42. He, T. C., Sparks, A. B., Rago, C., Hermeking, H., Zawel, L., da Costa, L. T., Morin, P. J., Vogelstein, B., and Kinzler, K. W. Identification of c-MYC as a target of the APC pathway. Science, 281: 1509-1512, 1998. 43. Shih, J. Y., Tsai, M. F., Chang, T. H., Chang, Y. L., Yuan, A., Yu, C. J., Lin, S. B., Liou, G. Y., Lee, M. L., Chen, J. J., Hong, T. M., Yang, S. C., Su, J. L., Lee, Y. C., and Yang, P. C. Transcription repressor slug promotes carcinoma invasion and predicts outcome of patients with lung adenocarcinoma. Clin Cancer Res, 11: 8070-8078, 2005. 44. del Barrio, M. G. and Nieto, M. A. Overexpression of Snail family members highlights their ability to promote chick neural crest formation. Development, 129: 1583-1593, 2002. 45. Savagner, P., Kusewitt, D. F., Carver, E. A., Magnino, F., Choi, C., Gridley, T., and Hudson, L. G. Developmental transcription factor slug is required for effective re-epithelialization by adult keratinocytes. J Cell Physiol, 202: 858-866, 2005. 46. Hajra, K. M., Chen, D. Y., and Fearon, E. R. The SLUG zinc-finger protein represses E-cadherin in breast cancer. Cancer Res, 62: 1613-1618, 2002. 47. Martinez-Estrada, O. M., Culleres, A., Soriano, F. X., Peinado, H., Bolos, V., Martinez, F. O., Reina, M., Cano, A., Fabre, M., and Vilaro, S. The transcription factors Slug and Snail act as repressors of Claudin-1 expression in epithelial cells. Biochem J, 394: 449-457, 2006. 48. Guo, W. and Giancotti, F. G. Integrin signalling during tumour progression. Nat Rev Mol Cell Biol, 5: 816-826, 2004. 49. Nieto, M. A. The snail superfamily of zinc-finger transcription factors. Nat Rev Mol Cell Biol, 3: 155-166, 2002. 50. Albertson, D. G. Gene amplification in cancer. Trends Genet, 22: 447-455, 2006. 51. Weir, B. A., Woo, M. S., Getz, G., Perner, S., Ding, L., Beroukhim, R., Lin, W. M., Province, M. A., Kraja, A., Johnson, L. A., Shah, K., Sato, M., Thomas, R. K., Barletta, J. A., Borecki, I. B., Broderick, S., Chang, A. C., Chiang, D. Y., Chirieac, L. R., Cho, J., Fujii, Y., Gazdar, A. F., Giordano, T., Greulich, H., Hanna, M., Johnson, B. E., Kris, M. G., Lash, A., Lin, L., Lindeman, N., Mardis, E. R., McPherson, J. D., Minna, J. D., Morgan, M. B., Nadel, M., Orringer, M. B., Osborne, J. R., Ozenberger, B., Ramos, A. H., Robinson, J., Roth, J. A., Rusch, V., Sasaki, H., Shepherd, F., Sougnez, C., Spitz, M. R., Tsao, M. S., Twomey, D., Verhaak, R. G., Weinstock, G. M., Wheeler, D. A., Winckler, W., Yoshizawa, A., Yu, S., Zakowski, M. F., Zhang, Q., Beer, D. G., Wistuba, II, Watson, M. A., Garraway, L. A., Ladanyi, M., Travis, W. D., Pao, W., Rubin, M. A., Gabriel, S. B., Gibbs, R. A., Varmus, H. E., Wilson, R. K., Lander, E. S., and Meyerson, M. Characterizing the cancer genome in lung adenocarcinoma. Nature, 450: 893-898, 2007. 52. Tian, Q., Feetham, M. C., Tao, W. A., He, X. C., Li, L., Aebersold, R., and Hood, L. Proteomic analysis identifies that 14-3-3zeta interacts with beta-catenin and facilitates its activation by Akt. Proc Natl Acad Sci U S A, 101: 15370-15375, 2004. 53. Bridges, D. and Moorhead, G. B. 14-3-3 proteins: a number of functions for a numbered protein. Sci STKE, 2005: re10, 2005. 54. Zhu, P., Sun, Y., Xu, R., Sang, Y., Zhao, J., Liu, G., Cai, L., Li, C., and Zhao, S. The interaction between ADAM 22 and 14-3-3zeta: regulation of cell adhesion and spreading. Biochem Biophys Res Commun, 301: 991-999, 2003. 55. Li, R., Wang, H., Bekele, B. N., Yin, Z., Caraway, N. P., Katz, R. L., Stass, S. A., and Jiang, F. Identification of putative oncogenes in lung adenocarcinoma by a comprehensive functional genomic approach. Oncogene, 25: 2628-2635, 2006. 56. Melnikow, E., Dornan, S., Sargent, C., Duszenko, M., Evans, G., Gunkel, N., Selzer, P. M., and Ullrich, H. J. Microarray analysis of Haemophilus parasuis gene expression under in vitro growth conditions mimicking the in vivo environment. Vet Microbiol, 110: 255-263, 2005. 57. Olshen, A. B., Venkatraman, E. S., Lucito, R., and Wigler, M. Circular binary segmentation for the analysis of array-based DNA copy number data. Biostatistics, 5: 557-572, 2004. 58. Chen, J. J., Yao, P. L., Yuan, A., Hong, T. M., Shun, C. T., Kuo, M. L., Lee, Y. C., and Yang, P. C. Up-regulation of tumor interleukin-8 expression by infiltrating macrophages: its correlation with tumor angiogenesis and patient survival in non-small cell lung cancer. Clin Cancer Res., 9: 729-737., 2003. 59. Tsai, M. F., Wang, C. C., Chang, G. C., Chen, C. Y., Chen, H. Y., Cheng, C. L., Yang, Y. P., Wu, C. Y., Shih, F. Y., Liu, C. C., Lin, H. P., Jou, Y. S., Lin, S. C., Lin, C. W., Chen, W. J., Chan, W. K., Chen, J. J., and Yang, P. C. A new tumor suppressor DnaJ-like heat shock protein, HLJ1, and survival of patients with non-small-cell lung carcinoma. J Natl Cancer Inst., 98: 825-838., 2006. 60. Denker, S. P. and Barber, D. L. Cell migration requires both ion translocation and cytoskeletal anchoring by the Na-H exchanger NHE1. J Cell Biol, 159: 1087-1096, 2002. 61. Rauch, B. H., Bretschneider, E., Braun, M., and Schror, K. Factor Xa releases matrix metalloproteinase-2 (MMP-2) from human vascular smooth muscle cells and stimulates the conversion of pro-MMP-2 to MMP-2: role of MMP-2 in factor Xa-induced DNA synthesis and matrix invasion. Circ Res, 90: 1122-1127, 2002. 62. Kel, A. E., Gossling, E., Reuter, I., Cheremushkin, E., Kel-Margoulis, O. V., and Wingender, E. MATCH: A tool for searching transcription factor binding sites in DNA sequences. Nucleic Acids Res, 31: 3576-3579, 2003. 63. Morrison, D. K. The 14-3-3 proteins: integrators of diverse signaling cues that impact cell fate and cancer development. Trends Cell Biol, 19: 16-23, 2009. 64. Liu, C. C., Lin, C. C., Chen, W. S., Chen, H. Y., Chang, P. C., Chen, J. J., and Yang, P. C. CRSD: a comprehensive web server for composite regulatory signature discovery. Nucleic Acids Res, 34: W571-577, 2006. 65. Nelson, W. J. and Nusse, R. Convergence of Wnt, beta-catenin, and cadherin pathways. Science, 303: 1483-1487, 2004. 66. Clark, E. S. and Weaver, A. M. A new role for cortactin in invadopodia: regulation of protease secretion. Eur J Cell Biol, 87: 581-590, 2008. 67. Niemantsverdriet, M., Wagner, K., Visser, M., and Backendorf, C. Cellular functions of 14-3-3 zeta in apoptosis and cell adhesion emphasize its oncogenic character. Oncogene, 27: 1315-1319, 2008. 68. Keshamouni, V. G., Michailidis, G., Grasso, C. S., Anthwal, S., Strahler, J. R., Walker, A., Arenberg, D. A., Reddy, R. C., Akulapalli, S., Thannickal, V. J., Standiford, T. J., Andrews, P. C., and Omenn, G. S. Differential protein expression profiling by iTRAQ-2DLC-MS/MS of lung cancer cells undergoing epithelial-mesenchymal transition reveals a migratory/invasive phenotype. J Proteome Res, 5: 1143-1154, 2006. 69. Thiery, J. P. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer, 2: 442-454, 2002. 70. Mazieres, J., He, B., You, L., Xu, Z., and Jablons, D. M. Wnt signaling in lung cancer. Cancer Lett, 222: 1-10, 2005. 71. Uematsu, K., He, B., You, L., Xu, Z., McCormick, F., and Jablons, D. M. Activation of the Wnt pathway in non small cell lung cancer: evidence of dishevelled overexpression. Oncogene, 22: 7218-7221, 2003. 72. Calvo, R., West, J., Franklin, W., Erickson, P., Bemis, L., Li, E., Helfrich, B., Bunn, P., Roche, J., Brambilla, E., Rosell, R., Gemmill, R. M., and Drabkin, H. A. Altered HOX and WNT7A expression in human lung cancer. Proc Natl Acad Sci U S A, 97: 12776-12781, 2000. 73. Kase, S., Sugio, K., Yamazaki, K., Okamoto, T., Yano, T., and Sugimachi, K. Expression of E-cadherin and beta-catenin in human non-small cell lung cancer and the clinical significance. Clin Cancer Res, 6: 4789-4796, 2000. 74. Sakai, D., Tanaka, Y., Endo, Y., Osumi, N., Okamoto, H., and Wakamatsu, Y. Regulation of Slug transcription in embryonic ectoderm by beta-catenin-Lef/Tcf and BMP-Smad signaling. Dev Growth Differ, 47: 471-482, 2005. 75. Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., Murray, T., and Thun, M. J. Cancer statistics, 2008. CA Cancer J Clin, 58: 71-96, 2008. 76. Rofstad, E. K. Microenvironment-induced cancer metastasis. Int J Radiat Biol, 76: 589-605, 2000. 77. Vaupel, P., Kallinowski, F., and Okunieff, P. Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res, 49: 6449-6465, 1989. 78. Schornack, P. A. and Gillies, R. J. Contributions of cell metabolism and H+ diffusion to the acidic pH of tumors. Neoplasia, 5: 135-145, 2003. 79. Xiao, H., Li, T. K., Yang, J. M., and Liu, L. F. Acidic pH induces topoisomerase II-mediated DNA damage. Proc Natl Acad Sci U S A, 100: 5205-5210, 2003. 80. Sarosi, G. A., Jr., Jaiswal, K., Herndon, E., Lopez-Guzman, C., Spechler, S. J., and Souza, R. F. Acid increases MAPK-mediated proliferation in Barrett''s esophageal adenocarcinoma cells via intracellular acidification through a Cl-/HCO3- exchanger. Am J Physiol Gastrointest Liver Physiol, 289: G991-997, 2005. 81. Fischer, B., Muller, B., Fisch, P., and Kreutz, W. An acidic microenvironment inhibits antitumoral non-major histocompatibility complex-restricted cytotoxicity: implications for cancer immunotherapy. J Immunother, 23: 196-207, 2000. 82. Park, H. J., Lyons, J. C., Ohtsubo, T., and Song, C. W. Acidic environment causes apoptosis by increasing caspase activity. Br J Cancer, 80: 1892-1897, 1999. 83. Chen, K. H., Tung, P. Y., Wu, J. C., Chen, Y., Chen, P. C., Huang, S. H., and Wang, S. M. An acidic extracellular pH induces Src kinase-dependent loss of beta-catenin from the adherens junction. Cancer Lett, 267: 37-48, 2008. 84. Rofstad, E. K., Mathiesen, B., Kindem, K., and Galappathi, K. Acidic extracellular pH promotes experimental metastasis of human melanoma cells in athymic nude mice. Cancer Res, 66: 6699-6707, 2006. 85. Kato, Y., Lambert, C. A., Colige, A. C., Mineur, P., Noel, A., Frankenne, F., Foidart, J. M., Baba, M., Hata, R., Miyazaki, K., and Tsukuda, M. Acidic extracellular pH induces matrix metalloproteinase-9 expression in mouse metastatic melanoma cells through the phospholipase D-mitogen-activated protein kinase signaling. J Biol Chem, 280: 10938-10944, 2005. 86. Xu, L., Fukumura, D., and Jain, R. K. Acidic extracellular pH induces vascular endothelial growth factor (VEGF) in human glioblastoma cells via ERK1/2 MAPK signaling pathway: mechanism of low pH-induced VEGF. J Biol Chem, 277: 11368-11374, 2002. 87. Fukumura, D., Xu, L., Chen, Y., Gohongi, T., Seed, B., and Jain, R. K. Hypoxia and acidosis independently up-regulate vascular endothelial growth factor transcription in brain tumors in vivo. Cancer Res, 61: 6020-6024, 2001. 88. Stock, C., Gassner, B., Hauck, C. R., Arnold, H., Mally, S., Eble, J. A., Dieterich, P., and Schwab, A. Migration of human melanoma cells depends on extracellular pH and Na+/H+ exchange. J Physiol, 567: 225-238, 2005. 89. Fish, E. M. and Molitoris, B. A. Alterations in epithelial polarity and the pathogenesis of disease states. N Engl J Med, 330: 1580-1588, 1994. 90. Liang, P. and MacRae, T. H. Molecular chaperones and the cytoskeleton. J Cell Sci, 110 ( Pt 13): 1431-1440, 1997. 91. Mounier, N. and Arrigo, A. P. Actin cytoskeleton and small heat shock proteins: how do they interact? Cell Stress Chaperones, 7: 167-176, 2002. 92. Bryantsev, A. L., Loktionova, S. A., Ilyinskaya, O. P., Tararak, E. M., Kampinga, H. H., and Kabakov, A. E. Distribution, phosphorylation, and activities of Hsp25 in heat-stressed H9c2 myoblasts: a functional link to cytoprotection. Cell Stress Chaperones, 7: 146-155, 2002. 93. Geum, D., Son, G. H., and Kim, K. Phosphorylation-dependent cellular localization and thermoprotective role of heat shock protein 25 in hippocampal progenitor cells. J Biol Chem, 277: 19913-19921, 2002. 94. Verschuure, P., Croes, Y., van den, I. P. R., Quinlan, R. A., de Jong, W. W., and Boelens, W. C. Translocation of small heat shock proteins to the actin cytoskeleton upon proteasomal inhibition. J Mol Cell Cardiol, 34: 117-128, 2002. 95. Wang, K. and Spector, A. alpha-crystallin stabilizes actin filaments and prevents cytochalasin-induced depolymerization in a phosphorylation-dependent manner. Eur J Biochem, 242: 56-66, 1996. 96. Landry, J. and Huot, J. Modulation of actin dynamics during stress and physiological stimulation by a signaling pathway involving p38 MAP kinase and heat-shock protein 27. Biochem Cell Biol, 73: 703-707, 1995. 97. Lavoie, J. N., Lambert, H., Hickey, E., Weber, L. A., and Landry, J. Modulation of cellular thermoresistance and actin filament stability accompanies phosphorylation-induced changes in the oligomeric structure of heat shock protein 27. Mol Cell Biol, 15: 505-516, 1995. 98. An, S. S., Fabry, B., Mellema, M., Bursac, P., Gerthoffer, W. T., Kayyali, U. S., Gaestel, M., Shore, S. A., and Fredberg, J. J. Role of heat shock protein 27 in cytoskeletal remodeling of the airway smooth muscle cell. J Appl Physiol, 96: 1701-1713, 2004. 99. Mairesse, N., Horman, S., Mosselmans, R., and Galand, P. Antisense inhibition of the 27 kDa heat shock protein production affects growth rate and cytoskeletal organization in MCF-7 cells. Cell Biol Int, 20: 205-212, 1996. 100. Liu, H. Y., MacDonald, J. I., Hryciw, T., Li, C., and Meakin, S. O. Human tumorous imaginal disc 1 (TID1) associates with Trk receptor tyrosine kinases and regulates neurite outgrowth in nnr5-TrkA cells. J Biol Chem, 280: 19461-19471, 2005. 101. Wang, C. C., Tsai, M. F., Dai, T. H., Hong, T. M., Chan, W. K., Chen, J. J., and Yang, P. C. Synergistic activation of the tumor suppressor, HLJ1, by the transcription factors YY1 and activator protein 1. Cancer Res, 67: 4816-4826, 2007. 102. Duncan, R. F. and Hershey, J. W. Protein synthesis and protein phosphorylation during heat stress, recovery, and adaptation. J Cell Biol, 109: 1467-1481, 1989. 103. Hornbeck, P. V., Chabra, I., Kornhauser, J. M., Skrzypek, E., and Zhang, B. PhosphoSite: A bioinformatics resource dedicated to physiological protein phosphorylation. Proteomics, 4: 1551-1561, 2004. 104. Diella, F., Cameron, S., Gemund, C., Linding, R., Via, A., Kuster, B., Sicheritz-Ponten, T., Blom, N., and Gibson, T. J. Phospho.ELM: a database of experimentally verified phosphorylation sites in eukaryotic proteins. BMC Bioinformatics, 5: 79, 2004. 105. Deaton, M. A., Bowman, P. D., Jones, G. P., and Powanda, M. C. Stress protein synthesis in human keratinocytes treated with sodium arsenite, phenyldichloroarsine, and nitrogen mustard. Fundam Appl Toxicol, 14: 471-476, 1990. 106. Pileggi, R. and Holland, G. R. The expression of heat shock protein 70 in the dental pulp following trauma. Dent Traumatol, 25: 426-428, 2009. 107. Yang, J. and Tower, J. Expression of hsp22 and hsp70 transgenes is partially predictive of drosophila survival under normal and stress conditions. J Gerontol A Biol Sci Med Sci, 64: 828-838, 2009. 108. Sontag, W. and Kruglikov, I. L. Expression of heat shock proteins after ultrasound exposure in HL-60 cells. Ultrasound Med Biol, 35: 1032-1041, 2009. 109. Chaudhuri, S. and Smith, P. G. Cyclic strain-induced HSP27 phosphorylation modulates actin filaments in airway smooth muscle cells. Am J Respir Cell Mol Biol, 39: 270-278, 2008. 110. Trepat, X., Deng, L., An, S. S., Navajas, D., Tschumperlin, D. J., Gerthoffer, W. T., Butler, J. P., and Fredberg, J. J. Universal physical responses to stretch in the living cell. Nature, 447: 592-595, 2007. 111. Izawa, I., Nishizawa, M., Ohtakara, K., Ohtsuka, K., Inada, H., and Inagaki, M. Identification of Mrj, a DnaJ/Hsp40 family protein, as a keratin 8/18 filament regulatory protein. J Biol Chem, 275: 34521-34527, 2000. 112. Yamazaki, D., Kurisu, S., and Takenawa, T. Regulation of cancer cell motility through actin reorganization. Cancer Sci, 96: 379-386, 2005. 113. Yeatman, T. J. A renaissance for SRC. Nat Rev Cancer, 4: 470-480, 2004. 114. Giaccone, G. and Zucali, P. A. Src as a potential therapeutic target in non-small-cell lung cancer. Ann Oncol, 19: 1219-1223, 2008. 115. Warmuth, M., Damoiseaux, R., Liu, Y., Fabbro, D., and Gray, N. SRC family kinases: potential targets for the treatment of human cancer and leukemia. Curr Pharm Des, 9: 2043-2059, 2003. 116. Boggon, T. J. and Eck, M. J. Structure and regulation of Src family kinases. Oncogene, 23: 7918-7927, 2004. 117. Irby, R. B., Mao, W., Coppola, D., Kang, J., Loubeau, J. M., Trudeau, W., Karl, R., Fujita, D. J., Jove, R., and Yeatman, T. J. Activating SRC mutation in a subset of advanced human colon cancers. Nat Genet, 21: 187-190, 1999. 118. Summy, J. M. and Gallick, G. E. Src family kinases in tumor progression and metastasis. Cancer Metastasis Rev, 22: 337-358, 2003. 119. Boyer, B., Bourgeois, Y., and Poupon, M. F. Src kinase contributes to the metastatic spread of carcinoma cells. Oncogene, 21: 2347-2356, 2002. 120. Wei, L., Yang, Y., Zhang, X., and Yu, Q. Altered regulation of Src upon cell detachment protects human lung adenocarcinoma cells from anoikis. Oncogene, 23: 9052-9061, 2004. 121. Masaki, T., Igarashi, K., Tokuda, M., Yukimasa, S., Han, F., Jin, Y. J., Li, J. Q., Yoneyama, H., Uchida, N., Fujita, J., Yoshiji, H., Watanabe, S., Kurokohchi, K., and Kuriyama, S. pp60c-src activation in lung adenocarcinoma. Eur J Cancer, 39: 1447-1455, 2003. 122. Zhang, J., Kalyankrishna, S., Wislez, M., Thilaganathan, N., Saigal, B., Wei, W., Ma, L., Wistuba, II, Johnson, F. M., and Kurie, J. M. SRC-family kinases are activated in non-small cell lung cancer and promote the survival of epidermal growth factor receptor-dependent cell lines. Am J Pathol, 170: 366-376, 2007. 123. Hutchison, K. A., Brott, B. K., De Leon, J. H., Perdew, G. H., Jove, R., and Pratt, W. B. Reconstitution of the multiprotein complex of pp60src, hsp90, and p50 in a cell-free system. J Biol Chem, 267: 2902-2908, 1992. 124. Pratt, W. B. The role of heat shock proteins in regulating the function, folding, and trafficking of the glucocorticoid receptor. J Biol Chem, 268: 21455-21458, 1993. 125. Bohen, S. P., Kralli, A., and Yamamoto, K. R. Hold ''em and fold ''em: chaperones and signal transduction. Science, 268: 1303-1304, 1995. 126. Dey, B., Caplan, A. J., and Boschelli, F. The Ydj1 molecular chaperone facilitates formation of active p60v-src in yeast. Mol Biol Cell, 7: 91-100, 1996. 127. Kurzik-Dumke, U., Gundacker, D., Renthrop, M., and Gateff, E. Tumor suppression in Drosophila is causally related to the function of the lethal(2) tumorous imaginal discs gene, a dnaJ homolog. Dev Genet, 16: 64-76, 1995. 128. Kim, S. W., Chao, T. H., Xiang, R., Lo, J. F., Campbell, M. J., Fearns, C., and Lee, J. D. Tid1, the human homologue of a Drosophila tumor suppressor, reduces the malignant activity of ErbB-2 in carcinoma cells. Cancer Res, 64: 7732-7739, 2004. 129. Kim, S. W., Hayashi, M., Lo, J. F., Fearns, C., Xiang, R., Lazennec, G., Yang, Y., and Lee, J. D. Tid1 negatively regulates the migratory potential of cancer cells by inhibiting the production of interleukin-8. Cancer Res, 65: 8784-8791, 2005. 130. Rush, J., Moritz, A., Lee, K. A., Guo, A., Goss, V. L., Spek, E. J., Zhang, H., Zha, X. M., Polakiewicz, R. D., and Comb, M. J. Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat Biotechnol, 23: 94-101, 2005. 131. Fincham, V. J., Unlu, M., Brunton, V. G., Pitts, J. D., Wyke, J. A., and Frame, M. C. Translocation of Src kinase to the cell periphery is mediated by the actin cytoskeleton under the control of the Rho family of small G proteins. J Cell Biol, 135: 1551-1564, 1996. 132. Mitra, A., Menezes, M. E., Shevde, L. A., and Samant, R. S. DNAJB6 induces degradation of beta-catenin and causes partial reversal of mesenchymal phenotype. J Biol Chem, 285: 24686-24694. 133. Chou, T. Y., Chen, W. C., Lee, A. C., Hung, S. M., Shih, N. Y., and Chen, M. Y. Clusterin silencing in human lung adenocarcinoma cells induces a mesenchymal-to-epithelial transition through modulating the ERK/Slug pathway. Cell Signal, 21: 704-711, 2009. 134. Larue, L. and Bellacosa, A. Epithelial-mesenchymal transition in development and cancer: role of phosphatidylinositol 3'' kinase/AKT pathways. Oncogene, 24: 7443-7454, 2005. 135. Avizienyte, E. and Frame, M. C. Src and FAK signalling controls adhesion fate and the epithelial-to-mesenchymal transition. Curr Opin Cell Biol, 17: 542-547, 2005. 136. Ancevska-Taneva, N., Onoprishvili, I., Andria, M. L., Hiller, J. M., and Simon, E. J. A member of the heat shock protein 40 family, hlj1, binds to the carboxyl tail of the human mu opioid receptor. Brain Res, 1081: 28-33, 2006. 137. Chen, C. H., Lin, H., Chuang, S. M., Lin, S. Y., and Chen, J. J. Acidic stress facilitates tyrosine phosphorylation of HLJ1 to associate with actin cytoskeleton in lung cancer cells. Exp Cell Res, 316: 2910-2921. 138. Rahmani, Z. APRO4 negatively regulates Src tyrosine kinase activity in PC12 cells. J Cell Sci, 119: 646-658, 2006. 139. Chang, B. Y., Conroy, K. B., Machleder, E. M., and Cartwright, C. A. RACK1, a receptor for activated C kinase and a homolog of the beta subunit of G proteins, inhibits activity of src tyrosine kinases and growth of NIH 3T3 cells. Mol Cell Biol, 18: 3245-3256, 1998. 140. Li, S., Okamoto, T., Chun, M., Sargiacomo, M., Casanova, J. E., Hansen, S. H., Nishimoto, I., and Lisanti, M. P. Evidence for a regulated interaction between heterotrimeric G proteins and caveolin. J Biol Chem, 270: 15693-15701, 1995. 141. Oneyama, C., Hikita, T., Enya, K., Dobenecker, M. W., Saito, K., Nada, S., Tarakhovsky, A., and Okada, M. The lipid raft-anchored adaptor protein Cbp controls the oncogenic potential of c-Src. Mol Cell, 30: 426-436, 2008. 142. Zhou, J., Scholes, J., and Hsieh, J. T. Characterization of a novel negative regulator (DOC-2/DAB2) of c-Src in normal prostatic epithelium and cancer. J Biol Chem, 278: 6936-6941, 2003. 143. Frame, M. C. Src in cancer: deregulation and consequences for cell behaviour. Biochim Biophys Acta, 1602: 114-130, 2002. 144. Bolos, V., Gasent, J. M., Lopez-Tarruella, S., and Grande, E. The dual kinase complex FAK-Src as a promising therapeutic target in cancer. Onco Targets Ther, 3: 83-97.en_US
dc.description.abstract肺癌是近年來具有高發生率和極高死亡率之惡性腫瘤,轉移(metastasis)是癌症進程中導致病患死亡的主因。癌細胞侵襲(invasion)是轉移的起始步驟,非侵襲性的腫瘤細胞經由降低細胞黏附因子,失去細胞極性並使細胞骨架重組而造成上皮-間葉的轉變作用(epithelial-mesenchymal transition,EMT),成為具轉移能力的癌細胞。研究指出透過許多訊息傳遞路徑,包括 EGF、Wnt、Src signaling的活化導致特定的轉錄因子大量表現而引發EMT造成癌轉移。為找尋新的癌轉移相關基因,實驗室先前分別以基因體雜合微陣列 (array-CGH)及基因表現晶片(cDNA microarray),發現具有調控轉移潛力的YWHAZ基因與新的抑癌基因HLJ1,然而兩者在肺癌轉移的分子機制目前並不清楚。為研究YWHAZ與HLJ1調控EMT的角色與機制,本論文分成三個部份探討。在第一部份主要探討YWHAZ蛋白引發肺癌細胞EMT與invadopodia形成之重要性。結果顯示YWHAZ可抑制β-catenin泛素化(ubiquitination)進而活化其訊息傳遞,並在核內形成YWHAZ/TCF4/β-catenin複合體結合至slug的啟動子上而誘導EMT之產生。此外, YWAHZ的Y178磷酸化之後能與 Src結合,並增加Src活性、MMP2分泌與促進invadopodia形成,說明Y178是YWHAZ蛋白具有致癌特性的重要胺基酸。第二部份針對腫瘤酸性微環境,探討HLJ1的酪胺酸磷酸化與骨架蛋白的交互作用。我們發現HLJ1為酪胺酸磷酸化蛋白,Y172的磷酸化會影響HLJ1在細胞內的分布,也說明了酸性逆境下經由增加HLJ1的磷酸化活性與肌動蛋白結合進而抑制癌細胞的移動能力。第三部份為研究HLJ1與Src之交互作用,並鑑定兩者結合的區域,以瞭解HLJ1調控EMT的機制。結果證明HLJ1透過抑制EMT的發生進而控制肺癌之轉移,接著我們發現HLJ1能結合至Src SH3及kinase區域 (domain),並且抑制Src的活化與其磷酸化下游的能力。更重要的是,我們發現HLJ1能干擾Src下游分子與訊息傳遞路徑包括FAK與β-catenin。另一方面,我們證實HLJ1在Y172的胺基酸位置可被Src誘導磷酸化,並對 HLJ1的抑癌活性相當重要。不僅如此,我們也確認HLJ1 的P301/P304是Src SH3結合區域 (binding motif),也是HLJ1蛋白具有抑癌特性的重要胺基酸。藉由以上的研究結果,期望可提供調控癌細胞EMT的分子機制,並希望對於癌症臨床治療有所貢獻。zh_TW
dc.description.abstractMetastasis is the major cause leading to mortality for lung cancer patients. In carcinomas, metastasis is a multiple-step process, the first of which is invasion. Cancer cells acquire their invasive capacity by undergoing phenotypic conversion referred to as epithelial–mesenchymal transition (EMT), which is mediated by various pathway including EGF、Wnt、Src signaling and contributes to metastasis. To obtain the novel metastasis-related genes, we used the microarray-based comparative genomic hybridization and affymetrix gene expression profiles to identify the potential candidates, YWHAZ and HLJ1, respectively. To investigate the roles of YWHAZ and HLJ1 in modulating epithelial-mesenchymal transition and cancer progression, three specific parts are included in this dissertation. In the first part, we investigated the importance of YWHAZ in inducing EMT and invadopodia formation. Our results demonstrated that oncogenic functions of YWHAZ are mediated, at least partly, by prevention of ubiquitination ofβ-catenin. Subsequently, the accumulated β-catenin activates β-catenin/TCF signalling and slug-mediated EMT pathway. On the other hand, YWHAZ associates with Src by its phosphorylation at Y178 and positive regulation of Src-induced podosome rings, causing MMP2 secretion and gelatin degradation. In the second part, we focused on the molecular mechanism of HLJ1 on suppressing migration of lung cancer cells in acidic microenvironment. We not only provide evidence that HLJ1 is a tyrosine phosphoprotein but also illustrate HLJ1 binding to actin cytoskeleton during acidic stress and tyrosine phosphorylation-dependent association with β-actin. Finally, the third part of this dissertation presents a new molecular mechanism in HLJ1-Src complex and illustrates an important role for HLJ1 to inhibit EMT. Our findings revealed that HLJ1 associates with Src and represses its activation as well as downstream signaling, including FAK and β-catenin. Meanwhile, we reveal the critical amino acids in HLJ1 for HLJ1-Src interaction and suppressor characteristic of HLJ1. Taken together, these efforts will enhance our understanding on the impact of YWHAZ and HLJ1 on modulation of EMT and may have important implications for future cancer enhancer and suppressor investigations.zh_TW
dc.description.tableofcontents誌謝 i 中文摘要 ii Abstract iii Table of Contents iv List of Figures vii List of Tables ix Abbreviation 1 Preface 3 Chapter I YWHAZ Synergistically Induces Epithelial–Mesenchymal Transition and Invadopodia Formation to Promote Cancer Progression 5 Abstract 6 Introduction 7 Methods 9 Results 19 YWHAZ associated with survival of lung cancer patients 19 YWHAZ is a potential oncogene in lung cancer 20 YWHAZ promotes tumorigenesis and metastasis in vivo 20 YWHAZ induces a neuron-like morphological change and EMT 21 YWHAZ activates slug expression through β-catenin/TCF signalling 22 YWHAZ associates with β-catenin to retard degradation of β-catenin via the ubiquitin-proteasome pathway 23 YWHAZ-β-catenin interaction promotes cancer invasion 24 YWHAZ mediates invadopodia formation and binds to Src by its Y178 phosphorylation 25 Y178 in YWHAZ is a pivotal site for YWHAZ-mediated invadopodia formation and oncogenic functions 26 Discussion 28 Figures 32 Tables 59 Chapter II Acidic stress facilitates tyrosine phosphorylation of HLJ1 to associate with actin cytoskeleton in lung cancer cells 65 Abstract 66 Introduction 67 Methods 69 Results 74 Acidic stress decreased cell migration and up-regulated HLJ1 protein in lung cancer cells 74 Increased tyrosine phosphorylation of HLJ1 by acidic pHe 75 Identification of the sub-cellular distribution of phospho-HLJ1 and its tyrosine-phosphorylated sites 76 Tyrosine phosphorylation of HLJ1 is critical to the interaction with actin cytoskeleton 77 Discussion 79 Figures 83 Chapter III HLJ1 Controls Epithelial-Mesenchymal Transition by Its Binding to Src and Suppressing Src Activation 94 Abstract 95 Introduction 96 Methods 98 Results 105 HLJ1 serves as a suppresser of epithelial-mesenchymal transition (EMT) 105 HLJ1 is a novel interacting protein with Src 105 HLJ1 expression controls Src membrane-targeting and Src activity 106 Src-FAK interaction and tyrosine phosphorylation of FAK were regulated by HLJ1 expression 107 Silence of HLJ1 expression promotes Src binding to β-catenin and nuclear accumulation of β-catenin 108 Full-length HLJ1 directly associates with kinase and SH3 domain of Src 109 Y172 phosphorylation of HLJ1 is crucial for HLJ1 in repressing Src-medicated invasion 110 P301/P304 motif in HLJ1 is essential for HLJ1-Src interaction and suppressor characteristic of HLJ1 111 Analysis of Src activity and HLJ1 expression in mammalian tissues 112 Discussion 114 Figures 119 Conclusion 140 References 141 Plasmid Map 156 Appendix 163 Figure I-1 Analysis of YWHAZ expression in lung cancer cell lines 32 Figure I-2 High YWHAZ expression is correlated with tumorigenesis and poor survival in lung cancer patients 34 Figure I-3 YWHAZ is a potential oncogene in lung cancer 36 Figure I-4 YWHAZ promotes tumorigenesis and metastasis in vivo 38 Figure I-5 YWHAZ induces a neuron-like morphological change and EMT 40 Figure I-6 YWHAZ activates slug expression through β-catenin/TCF signalling in lung cancer cells 43 Figure I-7 The complex of YWHAZ/β-catenin/TCF4 on slug promoter 45 Figure I-8 YWHAZ retards the degradation of β-catenin via the ubiquitin-proteasome pathway 48 Figure I-9 Disruption of YWHAZ and β-catenin complex reduces lung cancer invasion 50 Figure I-10 YWHAZ expression enhances gelatin degradation and formation of F-actin rings 52 Figure I-11 Y178 in YWHAZ is crucial for its binding to Src 54 Figure I-12 Y178 plays an important role for YWHAZ to promote invadopodia formation 55 Figure I-13 Y178 is required for YWHAZ to acquire oncogenic functions 56 Figure I-14 A hypothetical model for the role of YWHAZ in facilitating cancer progression 58 Figure II-1 Effects of acidic stress on lung cancer cell viability, migration, and morphology 83 Figure II-2 Up-regulation of HLJ1 protein by acidic stress 85 Figure II-3 Acidification-induced increase of tyrosine–phosphorylated HLJ1 86 Figure II-4 Identification of the sub-cellular distribution of phospho-HLJ1 and its tyrosine-phosphorylated sites 88 Figure II-5 The sub-cellular distribution of wild-type and mutant V5-HLJ1 protein in normal condition 90 Figure II-6 Acidic stress augments HLJ1 binding to actin cytoskeleton 91 Figure II-7 Tyrosine phosphorylation-dependent association of HLJ1 with β-actin 93 Figure III-1 HLJ1 expression suppresses lung cancer metastasis 119 Figure III-2 HLJ1 inhibits epithelial–mesenchymal transition (EMT) 120 Figure III-3 HLJ1 associates with Src in vivo and in vitro 121 Figure III-4 HLJ1 alters the cellular localization and activity of c-Src 123 Figure III-5 HLJ1 expression suppresses the membrane recruitment and activity of oncogenic Src 124 Figure III-6 Down-regulated tyrosine phosphorylation and Src-FAK interaction upon HLJ1 expression 126 Figure III-7 HLJ1 reduces tyrosine phosphorylation and nuclear accumulation of β-catenin 127 Figure III-8 Full-length HLJ1 directly associates with SH3 and kinase domain of Src 129 Figure III-9 Y172 of HLJ1 is a major phosphorylation site induced by Src 131 Figure III-10 Y172 of HLJ1 is crucial for HLJ1-Src interaction and invasionsuppression of HLJ1 133 Figure III-11 P301/P304 of HLJ1 is the binding site of Src-SH3 domain 134 Figure III-12 P301/P304 of HLJ1 is essential for HLJ1 to inhibit Src activity, tyrosine-phosphorylation levels and EMT 136 Figure III-13 Analysis of Src activity and HLJ1 expression in mammalian tissues 138 Figure III-14 A hypothetical model for the role of HLJ1 in suppressing cancer progression 139 Table 1 P values for log-rank test of each expression leve 59 Table 2 Summary of clinicopathologic features according to YWHAZ expression 60 Table 3 Summary of pathological incidence of lungs in mice by intravenous injection with YWHAZ-expressing cells or mock control 61 Table 4 Comparison of the incidence of tumorigenesis or metastasis between mock and YWHAZ transfectant in SCID mice by orthotopic lung implantation model 62 Table 5 Clinicopathologic characteristics of the NSCLC patients by YWHAZ expression 63 Table 6 EMT-related pathways involved in CL1-0 cells following YWHAZ gene introduction 64zh_TW
dc.subjectEpithelial-Mesenchymal Transitionen_US
dc.subjectLung canceren_US
dc.titleInvestigating the Roles of YWHAZ and HLJ1 in Modulating Epithelial-Mesenchymal Transition and Lung Cancer Progressionen_US
dc.typeThesis and Dissertationzh_TW
item.openairetypeThesis and Dissertation-
item.fulltextno fulltext-
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