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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 梁博煌 | zh_TW |
| dc.contributor.advisor | Po-Huang Liang | en |
| dc.contributor.author | 張蕴薰 | zh_TW |
| dc.contributor.author | Yun-Xun Chang | en |
| dc.date.accessioned | 2023-05-10T16:06:17Z | - |
| dc.date.available | 2023-11-09 | - |
| dc.date.copyright | 2023-05-10 | - |
| dc.date.issued | 2023 | - |
| dc.date.submitted | 2023-02-10 | - |
| dc.identifier.citation | Reference
1. Global health observatory: the data repository. Geneva: World Health Organization, 2017. (accessed 1 Jun 2017). 2. Rebecca, L.Siegel.; Kimberly, D.Miller.; Ahmedin Jemal. Cancer statistics, 2019. CA. Cancer J. Clin. 2019, 69(1), 7-34. 3. Adrienne, G.Waks.; Eric, P.Winer. Breast Cancer Treatment: A Review. JAMA. 2019, 321(3), 288-300. 4. Freddie, Bray.; Jacques, Ferlay.; Isabelle, Soerjomataram.; Rebecca, L.Siegel.; Lindsey, A.Torre.; Ahmedin, Jemal. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA. Cancer J. Clin. 2018, 68(6), 394-424. 5. Huang, C.Y.; Ju, D.T.; Chang, C.F.; Muralidhar, Reddy.P.; Velmurugan, B.K. A review on the effects of current chemotherapy drugs and natural agents in treating non–small cell lung cancer. Biomedicine (Taipei). 2017, 7(4), 23. 6. Prat, J.; Nomonde, M. Uterine sarcomas. Int. J. Gynecol. Obstet. 2015, 131, S105–S110. 7. Behzad, Mansoori.; Ali, Mohammadi.; Sadaf, Davudian.; Solmaz, Shirjang.; Behzad, Baradaran. The Different Mechanisms of Cancer Drug Resistance: A Brief Review. Adv. Pharm. Bull. 2017, 7(3), 339–348. 8. Nikolaou, M.; Pavlopoulou, A.; Georgakilas, A.G.; Kyrodimos, E. The challenge of drug resistance in cancer treatment: a current overview. Clin. Exp. Metastasis. 2018, 35(4), 309-318. 9. Gottesman, M.M.; Ludwig, J.; Xia, D. Szakács, G. Defeating drug resistance in cancer. Discov. Med. 2006, 6(31), 18-23. 10. Burg, D.; Wielinga, P.; Zelcer, N.; Saeki, T.; Mulder, G.J.; Borst, P. Inhibition of the multidrug resistance protein 1 (MRP1) by peptidomimetic glutathione-conjugate analogs. Mol. Pharmacol. 2002, 62(5), 1160–1166. 11. Zahreddine, H.; Borden, K.L. Mechanisms and insights into drug resistance in cancer. Front. Pharmacol. 2013, 4:28. 12. Bashar, E.; Jessica, B.; Yasna, J.; Barbara, J.; Taher, S. Biophysics of Tumor Microenvironment and Cancer Metastasis - A Mini Review. Comput. Struct. Biotechnol. J. 2018, 16, 279-287. 13. Steeg, P.S. Targeting metastasis. Nature Reviews Cancer. 2016, 16, 201–218. 14. Soussan, I. Emerging insights into the biology of metastasis: A review article. Iran. J. Basic. Med. Sci. 2019, 22(8), 833–847. 15. Irani, S.; Moshref, M.; Lotfi, A. Metastasis of a gastric adenocarcinoma to the mandible:A case report. Oral. Oncol. extra. 2004, 40, 85–87. 16. Anushka, D.; Robert, A.W.New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer. Nature Reviews Molecular Cell Biology. 2019, 20, 69-84. 17. Zhang, Y.; Robert, A.W. Epithelial-to-mesenchymal transition in cancer: complexity and opportunities. Frontiers of Medicine volume. 2018, 12, 361–373. 18. Tyedmers, J.; Mogk, A.; Bukau, B. Cellular strategies for controlling protein aggregation. Nat. Rev. Mol. Cell Biol. 2010, 11, 777-788. 19. Bigotti, M.G.; Clarke, A. R. Chaperonins: The hunt for the Group II mechanism. Arch. Biochem. Biophys. 2008, 474, 331-339. 20. Horwich, A.L.; Fenton W.A; Chapman, E.; Farr, G.W. Two families of chaperonin: physiology and mechanism. Review. Annu. Rev. Cell. Dev. Biol. 2007, 23, 115-145. 21. Spiess, C.; Meyer, A.S.; Reissmann, S.; Frydman, J. Mechanism of the eukaryotic chaperonin: protein folding in the chamber of secrets. Review. Trends. Cell. Biol. 2004, 14(11), 598-604. 22. Lin, P.; Sherman, F. The unique hetero-oligomeric nature of the subunits in the catalytic cooperativity of the yeast Cct chaperonin complex. Proc. Natl. Acad. Sci. USA. 1997, 94, 10780-10785. 23. Booth, C.R.; Meyer, A.S.; Cong, Y.; Topf, M.; Sali, A.; Ludtke, S.J.; Chiu, W.; Frydman, J. Mechanism of lid closure in the eukaryotic chaperonin TRiC/CCT. Nat. Struct. Mol. Biol. 2008, 15, 746-753. 24. Cong, Y.; Schröder, G.F.; Meyer, A.S.; Jakana, J.; Ma, B.; Dougherty, M.T.; Schmid, M.F.; Reissmann, S.; Levitt, M.; Ludtke, S. L.; Frydman, J.; Chiu, W. Symmetry-free cryo-EM structures of the chaperonin TRiC along its ATPase-driven conformational cycle. EMBO. J. 2002, 31, 720-730. 25. Yam, A.Y.; Xia, Y.; Lin, H.T.; Burlingame, A.; Gerstein, M.; Frydman, J. Defining the TRiC/CCT interactome links chaperonin function to stabilization of newly made proteins with complex topologies. Nat. Struct. Mol. Biol. 2008, 15, 1255-1262. 26. Camasses, A.; Bogdanova, A.; Shevchenko, A.; Zachariae, W. The CCT chaperonin promotes activation of the anaphase-promoting complex through the generation of functional Cdc20. Mol. Cell. 2002, 12, 87-100. 27. Huang, H.C.; Shi, J.; Orth, J.D.; Mitchison, T.J. Evidence that mitotic exit is a better cancer therapeutic target than spindle assembly. Cancer. Cell. 2009, 16, 347-358. 28. Nowak, M.A.; Komarova, N.L.; Sengupta, A.; Jallepalli, P.V.; Shih, IeM,; Vogelstein, B.; Lengauer, C. The role of chromosomal instability in tumor initiation. Proc. Natl. Acad. Sci. 2002, 99, 16226-16231. 29. Melki, R.; Batelier, G.; Soulié, S.; Williams, R.C.Jr. Cytoplasmic chaperonin containing TCP-1: structural and functional characterization. Biochemistry. 1997, 36, 5817-5826. 30. Won, K.A.; Schumacher, R.J.; Farr, G.W.; Horwich, A.L.; Reed, S.I. Maturationof human cyclin E requires the function of eukaryotic chaperonin CCT. Mol. Cell. Biol. 1998, 18, 7584-7589. 31. Nibbe, R.K.; Markowitz, S.; Myeroff, L.; Ewing, R.; Chance, M.R. Discovery and scoring of protein interaction subnetworks discriminative of late stage human colon cancer. Mol. Cell. Proteomics. 2009, 8, 827-845. 32. Yokota, S.; Yamamoto, Y.; Shimizu, K.; Momoi, H.; Kamikawa, T.; Yamaoka, Y.; Yanagi, H.; Yura, T.; Kubota, H. Increased expression of cytosolic chaperonin CCT in human hepatocellular and colonic carcinoma. Cell. Stress. Chaperones. 2001, 6, 345-350. 33. Alldinger, I.; Dittert, D.; Peiper, M.; Fusco, A.; Chiappetta, G.; Staub, E.; Lohr, M.; Jesnowski, R.; Baretton, G.; Ockert, D.; Saeger, H.D.; et al. Gene expression analysis of pancreatic cell lines reveals genes overexpressed in pancreatic cancer. Pancreatology. 2005, 5, 370-379. 34. Cimmino, F.; Spano, D.; Capasso, M.; Zambrano, N.; Russo, R.; Zollo, M.; Iolascon, A. Comparative proteomic expression profile in all trans retinoic acid differentiated neuroblastoma cell line. J. Proteome. Res. 2006, 6, 2550-2564. 35. Zhao, M.; Spiess, M.; Johansson, H.J.; Olofsson, H.; Hu, J.; Lehtiö, J.; Strömblad, S. Identification of the PAK4 interactome reveals PAK4 phosphorylation of N-WASP and promotion of Arp2/3-dependent actin polymerization. Oncotarget 2017, 8, 77061–77074. 36. Brackley, K.I.; Grantham, J. Interactions between the actin filament capping and severing protein gelsolin and the molecular chaperone CCT: Evidence for nonclassical substrate. Cell Stress Chaperones 2011, 16, 173–179. 37. Trinidad, A.G.; Muller, P.A.; Cuellar, J.; Klejnot, M.; Nobis, M.; Valpuesta, J.M.; Vousden, K.H. Interaction of p53 with the CCT complex promotes protein folding and wild-type p53 activity. Mol. Cell 2013, 50, 805–817. 38. Tracy, C.M.; Gray, A.J.; Cuéllar, J.; Shaw, T.S.; Howlett, A.C.; Taylor, R.M.; Prince, J.T.; Ahn, N.G.; Valpuesta, J.M.; Willardson, B.M. Programmed cell death protein 5 interacts with the cytosolic chaperonin containing tailless complex polypeptide 1 (CCT) to regulate β-tubulin folding. J. Biol. Chem. 2014, 289, 4490–4502. 39. Coghlin, C.; Carpenter, B.; Dundas, S.R.; Lawrie, L.C.; Telfer, C.; Murray, G.I. Characterization and over-expression of chaperonin t-complex proteins in colorectal cancer. J. Pathol. 2006, 210, 351–357. 40. Zou, Q.; Yang, Z.L.; Yuan, Y.; Li, J.H.; Liang, L.F.; Zeng, G.X.; Chen, S.L. Clinicopathological features and CCT2 and PDIA2 expression in gallbladder squamous/adenosquamous carcinoma and gallbladder adenocarcinoma. World J. Surg. Oncol. 2013, 11, 143. 41. Abe, Y.; Yoon, S.O.; Kubota, K.; Mendoza, M.C.; Gygi, S.P.; Blenis, J. p90 ribosomal S6 kinase and p70 ribosomal S6 kinase link phosphorylation of the eukaryotic chaperonin containing TCP-1 to growth factor, insulin, and nutrient signaling. J. Biol. Chem. 2009, 284, 14939–14948. 42. Murphy, L.; Henry, M.; Meleady, P.; Clynes, M.; Keenan, J. Proteomic investigation of taxol and taxotere resistance and invasiveness in a squamous lung carcinoma cell line. Biochim. Biophys. Acta 2008, 1784, 1184–1191. 43. Di, M.M.; Della, C.A.; Cicchillitti, L.; Del, B.P.; Urbani, A.; Ferlini, C.; Scambia, G.; Donati, M.B.; Rotilio, D. A proteomic approach to paclitaxel chemoresistance in ovarian cancer cell lines. Biochim. Biophys. Acta 2009, 1794, 225–236. 44. Logan, C.Y.; Nusse, R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004, 20, 781-810. 45. Clevers, H.; Wnt/beta-catenin signaling in development and disease. Cell. 2006, 127(3), 469-80. 46. Angers, S.; Moon, R.T. Proximal events in Wnt signal transduction. Nat. Rev. Mol. Cell. Biol. 2009, 10(7), 468-477. 47. Xi, H.; Mikhail, S.; Keiko, T.; Xin, Z. LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way. Development. 2004, 131(8), 1663-1677. 48. MacDonald, B.T.; Tamai, K.; He, X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev. Cell. 2009, 17(1), 9-26. 49. Bryan, T.M.; Keiko, T.; Xi, H. Wnt/β-catenin signaling: components, mechanisms, and diseases. Dev. Cell. 2009, 17(1), 9–26. 50. Julian, H.; Walter, B. Interplay of cadherin-mediated cell adhesion and canonical Wnt signaling. Cold. Spring. Harb. Perspect. Biol. 2010, 2(2), a002915. 51. Deveraux, Q.L.; Reed, J.C. IAP family proteins--suppressors of apoptosis. Genes Dev. 1999, 13(3), 239–252. 52. Evans, M.K.; Sauer, S.J.; Nath, S.; Robinson, T.J.; Morse, M.A.; Devi, G.R. X-linked inhibitor of apoptosis protein mediates tumor cell resistance to antibody-dependent cellular cytotoxicity. Cell Death Dis. 2016, 7(1), e2073. 53. Yang, Y.; Fang, S.; Jensen, J.P.; Weissman, A.M.; Ashwell, J.D. Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli. Science. 2000, 288(5467), 874–877. 54. Xiang, G.; Wen, X.; Wang, H.; Chen, K.; Liu, H. Expression of X-linked inhibitor of apoptosis protein in human colorectal cancer and its correlation with prognosis. J. Surg. Oncol. 2009, 100(8), 708–712. 55. Augello, C.; Caruso, L.; Maggioni, M.; Donadon, M.; Montorsi, M.; Santambrogio, R.; Torzilli, G.; Vaira, V.; Pellegrini, C.; Roncalli, M. Inhibitors of apoptosis proteins (IAPs) expression and their prognostic significance in hepatocellular carcinoma. BMC Cancer. 2009, 9, 125. 56. Xu, Y.C.; Liu, Q.; Dai, J.Q.; Yin, Z.Q.; Tang, L.; Ma, Y.; Lin, X.L.; Wang, H.X. Tissue microarray analysis of X-linked inhibitor of apoptosis (XIAP) expression in breast cancer patients. Med. Oncol. 2014, 31(3), 764. 57. Lin, Y.F.; Tsai, W.P.; Liu, H.G.; Liang, P.H. Intracellular beta-tubulin/chaperonin containing TCP1-beta complex serves as a novel chemotherapeutic target against drug-resistant tumors. Cancer Res. 2009, 69, 6879–6888. 58. Lin, Y.F.; Lee, Y.F.; Liang, P.H. Targeting β-tubulin: CCT-β complexes incurs Hsp90- and VCP-related protein degradation and induces ER stress-associated apoptosis by triggering capacitative Ca2+ entry, mitochondrial perturbation and caspase overactivation. Cell Death Dis. 2012, 3, e434. 59. Liu, Y.J.; Kumar, V.; Lin, Y.F.; Liang, P.H. Disrupting CCT-β: β-tubulin selectively kills CCT-β overexpressed cancer cells through MAPKs activation. Cell Death Dis. 2017, 8, e3052. 60. Liu, Y.J.; Chang, Y.J.; Kuo, Y.T.; Liang, P.H. Targeting β-tubulin/CCT-β complex induces apoptosis and suppresses migration and invasion of highly metastatic lung adenocarcinoma. Carcinogenesis 2020, 41, 699–710. 61. Toth, M.; Sohail, A.; Fridman, R. Assessment of gelatinases (MMP-2 and MMP-9) by gelatin zymography. Methods Mol. Biol. 2012, 878, 121–135. 62. Silva, K.L.; Souza, P.S.D.; Moraes, G.N.D.; Moellmann-Coelho, A.; Vasconcelos, F.D.C.; Maia, R.C. XIAP and P-glycoprotein co-expression is related to imatinib resistance in chronic myeloid leukemia cells. Leukemia Research. 2013, 37, 1350–1358. 63. Nestal, de.M.G.; Delbue, D.; Silva, K.L.; Robaina, M.C.; Khongkow, P.; Gomes, A.R.; Zona, S.; Crocamo, S.; Mencalha, A.L.; Magalhães, L.M.; Lam, E.W. et al. FOXM1 targets XIAP and Survivin to modulate breast cancer survival and chemoresistance. Cell. Signal. 2015, 27, 2496-2505. 64. Shen, D.Y.; Zhang, W.; Zeng, X.; Liu, C.Q. Inhibition of Wnt/β-catenin signaling downregulates P-glycoprotein and reverses multi-drug resistance of cholangiocarcinoma. Cancer. Sci. 2013, 104,1303–1308. 65. Valery, V.; Lilia, T.; Francesc, M.; Roberto, G. Targeting Wnt/β-catenin pathway in hepatocellular carcinoma treatment. World. J. Gastroenterol. 2016, 22, 823-832. 66. Kim, J.H.; Cho, E.B.; Lee, J.; Jung, O.; Ryu, B.J.; Kim, S.H.; Cho, J.Y.; Ryou, C.; Lee, S.Y. Emetine inhibits migration and invasion of human non-small-cell lung cancer cells via regulation of ERK and p38 signaling pathways. Chem. Biol. Interact. 2015, 242, 25-33. 67. Chen, Y.Y.; Liu, F.C.; Chou, P.Y.; Chien, Y.C.; Chang, W.S.; Huang, G.J.; Wu, C.H.; Sheu, M.J. Ethanol extracts of fruiting bodies of Antrodia cinnamomea suppress CL1-5 human lung adenocarcinoma cells migration by inhibiting matrix metalloproteinase-2/9 through ERK, JNK, p38, and PI3K/Akt signaling pathways. Evid. Based Complement. Alternat. Med. 2012, 2012, 378415. 68. Mehrotra, S.; Languino, L.R.; Raskett, C.M.; Mercurio, A.M.; Dohi, T.; Altieri, D.C. IAP regulation of metastasis. Cancer Cell 2010, 17, 53–64. 69. Hehlgans, S.; Petraki, C.; Reichert, S.; Cordes, N.; Rödel, C.; Rödel, F. Double targeting of Survivin and XIAP radiosensitizes 3D grown human colorectal tumor cells and decreases migration. Radiother. Oncol. 2013, 108, 32–39. 70. Chai, J.; Shiozaki, E.; Srinivasula, S.M.; Wu, Q.; Datta, P.; Alnemri, E.S.; Shi, Y. Structural basis of caspase-7 inhibition by XIAP. Cell 2001, 104, 769–780. 71. Riedl, S.J.; Renatus, M.; Schwarzenbacher, R.; Zhou, Q.; Sun, C.; Fesik, S.W.; Liddington, R.C.; Salvesen, G.S. Structural basis for the inhibition of caspase-3 by XIAP. Cell 2001, 104, 791–800. 72. Shiozaki, E.N.; Chai, J.; Rigotti, D.J.; Riedl, S.J.; Li, P.; Srinivasula, S.M.; Alnemri, E.S.; Fairman, R.; Shi, Y. Mechanism of XIAP-mediated inhibition of caspase-9. Mol. Cell 2003, 11, 519–527. 73. Notarbartolo, M.; Cervello, M.; Poma, P.; Dusonchet, L.; Meli, M.; D’Alessandro, N. Expression of the IAPs in multidrug resistant tumor cells. Oncol. Rep. 2004, 11, 133–136. 74. Schimmer, A.D.; Welsh, K.; Pinilla, C.; Wang, Z.; Krajewska, M.; Bonneau, M.J.; Pedersen, I.M.; Kitada, S.; Scott, F.L.; Bailly-Maitre, B.; et al. Small-molecule antagonists of apoptosis suppressor XIAP exhibit broad antitumor activity. Cancer Cell 2004, 5, 25–35. 75. Miyamoto, M.; Takano, M.; Iwaya, K.; Shinomiya, N.; Kato, M.; Aoyama, T.; Sasaki, N.; Goto, T.; Suzuki, A.; Hitrata, J.; et al. X-chromosome-linked inhibitor of apoptosis as a key factor for chemoresistance in clear cell carcinoma of the ovary. Br. J. Cancer 2014, 110, 2881–2886. 76. Nestal de Moraes, G.; Delbue, D.; Silva, K.L.; Robaina, M.C.; Khongkow, P.; Gomes, A.R.; Zona, S.; Crocamo, S.; Mencalha, A.L.; Magalhães, L.M.; et al. FOXM1 targets XIAP and Survivin to modulate breast cancer survival and chemoresistance. Cell Signal. 2015, 27, 2496–2505. 77. Sun, M.; Meares, G.; Song, L.; Jope, R.S. XIAP associates with GSK3 and inhibits the promotion of intrinsic apoptotic signaling by GSK3. Cell Signal. 2009, 21, 1857–1865. 78. Hanson, A.J.; Wallace, H.A.; Freeman, T.J.; Beauchamp, R.D.; Lee, L.A.; Lee, E. XIAP monoubiquitylates Groucho/TLE to promote canonical Wnt signaling. Mol. Cell 2012, 45, 619–628. 79. Ng, V.H.; Hang, B.I.; Sawyer, L.M.; Neitzel, L.R.; Crispi, E.E.; Rose, K.L.; Popay, T.M.; Zhong, A.; Lee, L.A.; Tansey, W.P.; et al. Phosphorylation of XIAP at threonine 180 controls its activity in Wnt signaling. J. Cell Sci. 2018, 131, jcs210575. 80. Silva, K.L.; de Souza, P.S.; Nestal de Moraes, G.; Moellmann-Coelho, A.; Vasconcelos, F.d.C.; Maia, R.C. XIAP and P-glycoprotein co-expression is related to imatinib resistance in chronic myeloid leukemia cells. Leuk. Res. 2013, 37, 1350–1358. 81. Noda, T.; Nagano, H.; Takemasa, I. Activation of Wnt/β-catenin signaling pathway induces chemoresistance to interferon-α/5-fluorouracil combination therapy for hepatocellular carcinoma. Br. J. Cancer 2009, 100, 1647–1658. 82. Chikazawa, N.; Tanaka, H.; Tasaka, T.; Nakamura, M.; Tanaka, M.; Onishi, H.; Katano, M. Inhibition of Wnt signaling pathway decreases chemotherapy-resistant side-population colon cancer cells. Anticancer Res. 2010, 30, 2041–2048. 83. Cao, J.; Ma, J.; Sun, L.; Li, J.; Qin, T.; Zhou, C.; Cheng, L.; Chen, K.; Qian, W.; Duan, W.; et al. Targeting glypican-4 overcomes 5-FU resistance and attenuates stem cell-like properties via suppression of Wnt/β-catenin pathway in pancreatic cancer cells. J. Cell Biochem. 2018, 119, 9498–9512. 84. Shen, D.Y.; Zhang, W.; Zeng, X.; Liu, C.Q. Inhibition of Wnt/β-catenin signaling downregulates P-glycoprotein and reverses multi-drug resistance of cholangiocarcinoma. Cancer Sci. 2013, 104, 1303–1308. 85. Stewart, D.J. Wnt signaling pathway in non-small cell lung cancer. J. Natl. Cancer Inst. 2014, 106, djt356. 86. Yao, H.; Ashihara, E.; Maekawa, T. Targeting the Wnt/β-catenin signaling pathway in human cancers. Expert Opin. Ther. Targets 2011, 15, 873–887. 87. Ryan, B.M.; O’Donovan, N.; Duffy, M.J. Survivin: A new target for anti-cancer therapy. Cancer Treat. Rev. 2009, 35, 553–562. 88. Lu, R.; Bian, F.; Zhang, X.; Qi, H.; Chuang, E.Y.; Pflugfelder, S.C.; Li, D.Q. The beta-catenin/Tcf4/survivin signaling maintains a less differentiated phenotype and high proliferative capacity of human corneal epithelial progenitor cells. Int. J. Biochem. Cell Biol. 2011, 43, 751–759. 89. Kenneth, N.S.; Duckett, C.S. IAP proteins: Regulators of cell migration and development. Curr. Opin. Cell Biol. 2012, 24, 871–875. 90. Huang, C.L.; Liu, D.; Ishikawa, S.; Nakashima, T.; Nakashima, N.; Yokomise, H.; Kadota, K.; Uenoc, M. Wnt1 overexpression promotes tumour progression in non-small cell lung cancer. Eur. J. Cancer 2008, 44, 2680–2688. 91. Teng, Y.; Wang, X.; Wang, Y.; Ma, D. Wnt/beta-catenin signaling regulates cancer stem cells in lung cancer A549 cells. Biochem. Biophys. Res. Commun. 2010, 392, 373–379. 92. Jang, G.B.; Kim, J.Y.; Cho, S.D.; Park, K.S.; Jung, J.Y.; Lee, H.Y.; Hong, I.S.; Nam, J.S. Blockade of Wnt/β-catenin signaling suppresses breast cancer metastasis by inhibiting CSC-like phenotype. Sci. Rep. 2015, 5, 12465. 93. Pacheco-Pinedo, E.C.; Durham, A.C.; Stewart, K.M.; Goss, A.M.; Lu, M.M.; Demayo, F.J.; Morrisey, E.E. Wnt/β-catenin signaling accelerates mouse lung tumorigenesis by imposing an embryonic distal progenitor phenotype on lung epithelium. J. Clin. Invest. 2011, 121, 1935–1945. 94. Prosperi, J.R.; Goss, K.H. A Wnt-ow of opportunity: Targeting the Wnt/β-catenin pathway in breast cancer. Curr. Drug Targets 2010, 11, 1074–1088. 95. Khramtsov, A.I.; Khramtsova, G.F.; Tretiakova, M.; Huo, D.; Olopade, O.I.; Goss, K.H. Wnt/β-catenin pathway activation is enriched in basal-like breast cancers and predicts poor outcome. Am. J. Pathol. 2010, 176, 2911–2920. 96. Geyer, F.C.; Lacroix-Triki, M.; Savage, K.; Arnedos, M.; Lambros, M.B.; MacKay, A.; Natrajan, R.; Reis-Filho, J.S. β-Catenin pathway activation in breast cancer is associated with triple-negative phenotype but not with CTNNB1 mutation. Mol. Pathol. 2011, 24, 209–231. 97. Bassiouni, R.; Nemec, K.N.; Iketani, A.; Flores, O.; Showalter, A.; Khaled, A.S.; Vishnubhotla, P.; Sprung, R.W. Jr; Kaittanis, C.; Perez, J.M.; et al. Chaperonin containing TCP-1 protein level in breast cancer cells predicts therapeutic application of a cytotoxic peptide. Clin. Cancer Res. 2017, 22, 4366–4379. 98. Deng, Y.R.; Chen, X.J.; Chen, W.; Wu, L.F.; Jiang, H.P.; Lin, D.; Wang, L.J.; Wang,W.; Guo, S.Q. Sp1 contributes to radioresistance of cervical cancer through targeting G2/M cell cycle checkpoint CDK1. Cancer Manag Res. 2019, 28, 11, 5835-5844. 99. Kubota, H.;Yokota, S.I.; Yanagi, T. Structures and co-regulated expression of the genes encoding mouse cytosolic chaperonin CCT subunits. European Journal of Biochemistry. 2001,25,492-500. 100. Chung, K.C.; Kim, S.M.; Rhang, S.; Lau, L.F.; Gomes, I. and Ahn, Y.S. Expression of immediate early gene pip92 during anisomycin-induced cell death is mediated by the JNK- and p38-dependent activation of Elk1. Eur. J. Biochem. 2000, 267, 4676-4684. 101. Singh, V.B.; Pavithra, L.; Chattopadhyay, S. and Pal, J.K. Stress-induced overexpression of the heme-regulated eIF-2alpha kinase is regulated by Elk-1 activated through ERK pathway. Biochem. Biophys. Res. Commun. 2009, 379, 710-715. 102. Duan, Q.; Pang, C.; Chang, N.; Zhang, J. and Liu, W. Overexpression of PAD4 suppresses drug resistance of NSCLC cell lines to gefitinib through inhibiting Elk1-mediated epithelial-mesenchymal transition. Oncol. Rep. 2016, 36, 551-558. 103. Kawahara, T.; Aljarah, A.K.; Shareef, H.K.; Inoue, S.; Ide, H.; Patterson, J.D.; Kashiwagi, E.; Han, B.; Li, Y.; Zheng, Y. and Miyamoto, H. Silodosin inhibits prostate cancer cell growth via ELK1 inactivation and enhances the cytotoxic activity of gemcitabine. Prostate. 2016, 76, 744-756. 104. Kawahara, T.; Ide, H.; Kashiwagi, E.; Patterson, J.D.; Inoue, S.; Shareef, H.K.; Aljarah, A.K.; Zheng, Y.; Baras, A.S. and Miyamoto, H. Silodosin inhibits the growth of bladder cancer cells and enhances the cytotoxic activity of cisplatin via ELK1 inactivation. Am. J. Cancer Res. 2015, 5, 2959-2968. 105. Tan, N.Y. and Khachigian, L.M. Sp1 phosphorylation and its regulation of gene transcription. Mol. Cell Biol. 2009, 29, 2483-2488 | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/87126 | - |
| dc.description.abstract | Chaperonin-containing TCP-1（CCT）是由八個亞基組成的伴侶蛋白，參與細胞內蛋白質折疊。在這裡，我們表明了CCT八個亞基水平的升高與癌症患者低生存率有顯著相關性，尤其是CCT-β 的過度表現造成癌症患者較低生存率。在三陰性乳腺癌細胞株MDA-MB-231和非小細胞肺癌細胞株CL1-5這兩個具有高度轉移特性的細胞株中可以發現CCT-β過度表現。而降低這些癌細胞中的CCT-β會導致抗凋亡蛋白（例如XIAP）水平降低，以及抑制Ser473-AKT和GSK3的磷酸化，進而導致β-catenin入核減少。這些改變降低了細胞的化學抗性和遷移/侵襲能力。反之，CCT-β的過表達透過促進AKT-GSK3β-β-catenin和XIAP-Survivin途徑恢復了化學抗性和細胞遷移/侵襲能力。免疫共沉澱數據表明，CCT複合物可能直接結合並穩定XIAP和β-catenin。這項研究不僅闡明了CCT在化學抗性和轉移中的作用，也是當前癌症治療的兩個主要障礙，更能為CCT-β過表達的癌症提供了可能的治療策略。 | zh_TW |
| dc.description.abstract | Chaperonin containing t-complex 1 (CCT) is a chaperonin composed of eight subunits that participates in intracellular protein folding. Here, we showed that increased levels of subunits of CCT, particularly CCT-β, were significantly correlated with lower survival rates for cancer patients. Endogenously high expression of CCT-β was found in cancer cell lines, such as the triple-negative breast cancer cell line MDA-MB-231 and the highly metastatic non-small-cell lung cancer cell line CL1-5. Knocking down CCT-β in these cancer cells led to decreased levels of anti-apoptotic proteins, such as XIAP, as well as inhibited phosphorylation of Ser473-AKT and GSK3, resulting in decrease of the nucleus-entering form of β-catenin; these changes reduced the chemoresistance and migration/invasion of the cells. Conversely, overexpression of CCT-β recovered the chemoresistance and cell migration/invasion by promoting the AKT-GSK3β-β-catenin and XIAP-Survivin pathways. Coimmunoprecipitation data revealed that the CCT complex might directly bind and stabilize XIAP and β-catenin. This study not only elucidates the roles of CCT in chemoresistance and metastasis, which are two major obstacles for current cancer therapy, but also provides a possible therapeutic strategy against cancers with overexpressed CCT-β. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2023-05-10T16:06:17Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2023-05-10T16:06:17Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | Table of Contents
中文摘要 i Abstract ii Table of Contents iii Abbreviations vii 1. Introduction 1 1.1 Cancer 1 1.2 Drug resistance 2 1.3 Metastasis 3 1.4 Chaperonin containing t-complex 1 (CCT) 5 1.5 Wnt/β-catenin signaling pathway 7 1.6 X-linked inhibitor of apoptosis protein (XIAP) 8 1.7 Specificity protein 1 (Sp1) 9 1.8 Previous and the present studies 10 2. Materials and Methods 11 2.1 Reagents 11 2.2 Collection of Clinical Samples and Immunohistochemistry 12 2.3 Cell Culture 13 2.4 Plasmids and Cell Transfection 14 2.5 Western Blot Analysis 15 2.6 Coimmunoprecipitation Assay 16 2.7 Flow Cytometry Analysis 16 2.8 MTT Assay 16 2.9 Wound-Healing Assay 17 2.10 Matrigel Invasion Assay 17 2.11 Gelatin Zymography 18 2.12 Promoter reporter assay 19 2.13 Statistical Analysis 19 3. Result 19 3.1 Poor chemotherapy response of clinical cancer patients was associated with endogenous overexpression of CCT-β 19 3.2 Prognosis of clinical lung and breast cancer patients was associated with CCT-β 20 3.3 Chemoresistance of MDA-MB-231 and CL1-5 cells was associated with downregulation of CCT-β expression 20 3.4 Chemotherapy resistance in MDA-MB-231 and CL1-5 cells was associated with CCT-β overexpression 21 3.5 Relationship between CCT-β expression and X-linked inhibitor of apoptosis (XIAP) 22 3.6 Relationship between CCT-β and β-Catenin 23 3.7 Association of CCT-β expression with chemoresistance in MCF-7, 7TR, MES-SA, and MES-SA/Dx5 cells 24 3.8 Chemoresistance in MCF-7 and MES-SA cells was associated with upregulation of CCT-β expression 25 3.9 Downregulation of CCT-β expression in 7TR and MES-SA/Dx5 cells reduced drug resistance 25 3.10 Inhibition of invasion/migration of MDA-MB-231 and CL1-5 cells was associated with knockdown of CCT-β 26 3.11 Increased invasion/migration of MDA-MB-231 and CL1-5 cells was associated with upregulation of CCT-β expression 27 3.12 Altered cell morphology and reduced EMT marker levels were associated with knockdown of CCT-β 27 3.13 The activity and expression of MMP-2/9 were inhibited by knocking down CCT-β 28 3.14 The AKT-GSK3β-β-catenin pathway was inhibited for metastasis by knocking down CCT-β 29 3.15 The XIAP-Survivin pathway was downregulated by knocking down CCT-β to inhibit invasion 29 3.16 Relationship between CCT-β expression and Sp1, ELK1 in chemotherapy-resistant cancer cells 30 3.17 The Sp1 and ELK1 were reciprocally regulated by CCT-β in the cancer cells 32 4. Discussion 32 5. Future Studies 37 Figure 40 Supplementary Information 86 Reference 88 List of publication 103 Note for the originality of this thesis 103 | - |
| dc.language.iso | en | - |
| dc.subject | 伴侶蛋白 | zh_TW |
| dc.subject | 化學抗性 | zh_TW |
| dc.subject | CCT-β | zh_TW |
| dc.subject | 轉移 | zh_TW |
| dc.subject | 癌症治療 | zh_TW |
| dc.subject | CCT-β | en |
| dc.subject | chemoresistance | en |
| dc.subject | metastasis | en |
| dc.subject | chaperonin | en |
| dc.subject | cancer therapy | en |
| dc.title | 伴侶蛋白TCP-1透過AKT-GSK3β-β-Catenin和XIAP-Survivin途徑促進癌症的化學抗性和轉移 | zh_TW |
| dc.title | Chaperonin-Containing TCP-1 Promotes Cancer Chemoresistance and Metastasis through the AKT-GSK3β-β-Catenin and XIAP-Survivin Pathways | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 111-1 | - |
| dc.description.degree | 博士 | - |
| dc.contributor.oralexamcommittee | 蕭宏昇;冀宏源 ;陳世勳;林源峰 | zh_TW |
| dc.contributor.oralexamcommittee | Michael Hsiao;Hung-Yuan Chi;Shih-Hsun Chen;Yuan-Feng Lin | en |
| dc.subject.keyword | 伴侶蛋白,CCT-β,化學抗性,轉移,癌症治療, | zh_TW |
| dc.subject.keyword | chaperonin,CCT-β,chemoresistance,metastasis,cancer therapy, | en |
| dc.relation.page | 103 | - |
| dc.identifier.doi | 10.6342/NTU202300340 | - |
| dc.rights.note | 同意授權(限校園內公開) | - |
| dc.date.accepted | 2023-02-13 | - |
| dc.contributor.author-college | 生命科學院 | - |
| dc.contributor.author-dept | 生化科學研究所 | - |
| 顯示於系所單位： | 生化科學研究所 | |
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