請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/66513
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳瑞華 | |
dc.contributor.author | Yu-Min Lin | en |
dc.contributor.author | 林裕敏 | zh_TW |
dc.date.accessioned | 2021-06-17T00:39:56Z | - |
dc.date.available | 2014-02-16 | |
dc.date.copyright | 2012-02-16 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-01-19 | |
dc.identifier.citation | Reference
Aigner, A. (2011). MicroRNAs (miRNAs) in cancer invasion and metastasis: therapeutic approaches based on metastasis-related miRNAs. J Mol Med (Berl) 89, 445-457. Al-Mehdi, A.B., Tozawa, K., Fisher, A.B., Shientag, L., Lee, A., and Muschel, R.J. (2000). Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis. Nature medicine 6, 100-102. Asangani, I.A., Rasheed, S.A., Nikolova, D.A., Leupold, J.H., Colburn, N.H., Post, S., and Allgayer, H. (2008). MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 27, 2128-2136. Baffa, R., Fassan, M., Volinia, S., O'Hara, B., Liu, C.G., Palazzo, J.P., Gardiman, M., Rugge, M., Gomella, L.G., Croce, C.M., et al. (2009). MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets. The Journal of pathology 219, 214-221. Bartel, D.P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281-297. Berezikov, E., Chung, W.J., Willis, J., Cuppen, E., and Lai, E.C. (2007). Mammalian mirtron genes. Molecular cell 28, 328-336. Berx, G., and van Roy, F. (2009). Involvement of members of the cadherin superfamily in cancer. Cold Spring Harbor perspectives in biology 1, a003129. Betz, R.C., Planko, L., Eigelshoven, S., Hanneken, S., Pasternack, S.M., Bussow, H., Van Den Bogaert, K., Wenzel, J., Braun-Falco, M., Rutten, A., et al. (2006). Loss-of-function mutations in the keratin 5 gene lead to Dowling-Degos disease. American journal of human genetics 78, 510-519. Bhullar, J.S., Subhas, G., Silberberg, B., Tilak, J., Andrus, L., Decker, M., and Mittal, V.K. (2011). A novel nonoperative orthotopic colorectal cancer murine model using electrocoagulation. Journal of the American College of Surgeons 213, 54-60; discussion 60-51. Bialik, S., and Kimchi, A. (2004). DAP-kinase as a target for drug design in cancer and diseases associated with accelerated cell death. Seminars in cancer biology 14, 283-294. Bianchi, F., Hu, J., Pelosi, G., Cirincione, R., Ferguson, M., Ratcliffe, C., Di Fiore, P.P., Gatter, K., Pezzella, F., and Pastorino, U. (2004). Lung cancers detected by screening with spiral computed tomography have a malignant phenotype when analyzed by cDNA microarray. Clinical cancer research : an official journal of the American Association for Cancer Research 10, 6023-6028. Brembeck, F.H., and Rustgi, A.K. (2000). The tissue-dependent keratin 19 gene transcription is regulated by GKLF/KLF4 and Sp1. The Journal of biological chemistry 275, 28230-28239. Brennecke, J., Stark, A., Russell, R.B., and Cohen, S.M. (2005). Principles of microRNA-target recognition. PLoS biology 3, e85. Browning, K.S., Gallie, D.R., Hershey, J.W., Hinnebusch, A.G., Maitra, U., Merrick, W.C., and Norbury, C. (2001). Unified nomenclature for the subunits of eukaryotic initiation factor 3. Trends in biochemical sciences 26, 284. Burks, E.A., Bezerra, P.P., Le, H., Gallie, D.R., and Browning, K.S. (2001). Plant initiation factor 3 subunit composition resembles mammalian initiation factor 3 and has a novel subunit. The Journal of biological chemistry 276, 2122-2131. Cai, X., Hagedorn, C.H., and Cullen, B.R. (2004). Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 10, 1957-1966. Calin, G.A., and Croce, C.M. (2006). MicroRNA signatures in human cancers. Nature reviews Cancer 6, 857-866. Caulin, C., Salvesen, G.S., and Oshima, R.G. (1997). Caspase cleavage of keratin 18 and reorganization of intermediate filaments during epithelial cell apoptosis. The Journal of cell biology 138, 1379-1394. Caulin, C., Ware, C.F., Magin, T.M., and Oshima, R.G. (2000). Keratin-dependent, epithelial resistance to tumor necrosis factor-induced apoptosis. The Journal of cell biology 149, 17-22. Cavallaro, U. (2004). N-cadherin as an invasion promoter: a novel target for antitumor therapy? Curr Opin Investig Drugs 5, 1274-1278. Cavallaro, U., and Christofori, G. (2001). Cell adhesion in tumor invasion and metastasis: loss of the glue is not enough. Biochimica et biophysica acta 1552, 39-45. Cavallaro, U., and Christofori, G. (2004). Cell adhesion and signalling by cadherins and Ig-CAMs in cancer. Nature reviews Cancer 4, 118-132. Chambers, A.F., Groom, A.C., and MacDonald, I.C. (2002). Dissemination and growth of cancer cells in metastatic sites. Nature reviews Cancer 2, 563-572. Chang, E.C., and Schwechheimer, C. (2004). ZOMES III: the interface between signalling and proteolysis. Meeting on The COP9 Signalosome, Proteasome and eIF3. EMBO reports 5, 1041-1045. Chen, C.H., Wang, W.J., Kuo, J.C., Tsai, H.C., Lin, J.R., Chang, Z.F., and Chen, R.H. (2005). Bidirectional signals transduced by DAPK-ERK interaction promote the apoptotic effect of DAPK. The EMBO journal 24, 294-304. Chen, P.S., Su, J.L., Cha, S.T., Tarn, W.Y., Wang, M.Y., Hsu, H.C., Lin, M.T., Chu, C.Y., Hua, K.T., Chen, C.N., et al. (2011). miR-107 promotes tumor progression by targeting the let-7 microRNA in mice and humans. The Journal of clinical investigation 121, 3442-3455. Chen, X., Johns, D.C., Geiman, D.E., Marban, E., Dang, D.T., Hamlin, G., Sun, R., and Yang, V.W. (2001). Kruppel-like factor 4 (gut-enriched Kruppel-like factor) inhibits cell proliferation by blocking G1/S progression of the cell cycle. The Journal of biological chemistry 276, 30423-30428. Chen, X., Whitney, E.M., Gao, S.Y., and Yang, V.W. (2003). Transcriptional profiling of Kruppel-like factor 4 reveals a function in cell cycle regulation and epithelial differentiation. Journal of molecular biology 326, 665-677. Chen, Z.Y., Shie, J.L., and Tseng, C.C. (2002). Gut-enriched Kruppel-like factor represses ornithine decarboxylase gene expression and functions as checkpoint regulator in colonic cancer cells. The Journal of biological chemistry 277, 46831-46839. Choi, B.J., Cho, Y.G., Song, J.W., Kim, C.J., Kim, S.Y., Nam, S.W., Yoo, N.J., Lee, J.Y., and Park, W.S. (2006). Altered expression of the KLF4 in colorectal cancers. Pathology, research and practice 202, 585-589. Christoffersen, N.R., Silahtaroglu, A., Orom, U.A., Kauppinen, S., and Lund, A.H. (2007). miR-200b mediates post-transcriptional repression of ZFHX1B. RNA 13, 1172-1178. Cook, T., Gebelein, B., Belal, M., Mesa, K., and Urrutia, R. (1999). Three conserved transcriptional repressor domains are a defining feature of the TIEG subfamily of Sp1-like zinc finger proteins. The Journal of biological chemistry 274, 29500-29504. Coulombe, P.A., and Omary, M.B. (2002). 'Hard' and 'soft' principles defining the structure, function and regulation of keratin intermediate filaments. Current opinion in cell biology 14, 110-122. Czech, B., Zhou, R., Erlich, Y., Brennecke, J., Binari, R., Villalta, C., Gordon, A., Perrimon, N., and Hannon, G.J. (2009). Hierarchical rules for Argonaute loading in Drosophila. Molecular cell 36, 445-456. Damoc, E., Fraser, C.S., Zhou, M., Videler, H., Mayeur, G.L., Hershey, J.W., Doudna, J.A., Robinson, C.V., and Leary, J.A. (2007). Structural characterization of the human eukaryotic initiation factor 3 protein complex by mass spectrometry. Molecular & cellular proteomics : MCP 6, 1135-1146. Dang, D.T., Chen, X., Feng, J., Torbenson, M., Dang, L.H., and Yang, V.W. (2003). Overexpression of Kruppel-like factor 4 in the human colon cancer cell line RKO leads to reduced tumorigenecity. Oncogene 22, 3424-3430. De Martelaere, K., Lintermans, B., Haegeman, G., and Vanhoenacker, P. (2007). Novel interaction between the human 5-HT7 receptor isoforms and PLAC-24/eIF3k. Cellular signalling 19, 278-288. Denk, H., and Lackinger, E. (1986). Cytoskeleton in liver diseases. Seminars in liver disease 6, 199-211. Deryugina, E.I., Zijlstra, A., Partridge, J.J., Kupriyanova, T.A., Madsen, M.A., Papagiannakopoulos, T., and Quigley, J.P. (2005). Unexpected effect of matrix metalloproteinase down-regulation on vascular intravasation and metastasis of human fibrosarcoma cells selected in vivo for high rates of dissemination. Cancer research 65, 10959-10969. Dinsdale, D., Lee, J.C., Dewson, G., Cohen, G.M., and Peter, M.E. (2004). Intermediate filaments control the intracellular distribution of caspases during apoptosis. The American journal of pathology 164, 395-407. Du, C., Fang, M., Li, Y., Li, L., and Wang, X. (2000). Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102, 33-42. Duursma, A.M., Kedde, M., Schrier, M., le Sage, C., and Agami, R. (2008). miR-148 targets human DNMT3b protein coding region. RNA 14, 872-877. Ebert, M.P., Mooney, S.H., Tonnes-Priddy, L., Lograsso, J., Hoffmann, J., Chen, J., Rocken, C., Schulz, H.U., Malfertheiner, P., and Lofton-Day, C. (2005). Hypermethylation of the TPEF/HPP1 gene in primary and metastatic colorectal cancers. Neoplasia 7, 771-778. Egeblad, M., and Werb, Z. (2002). New functions for the matrix metalloproteinases in cancer progression. Nature reviews Cancer 2, 161-174. Esau, C., Kang, X., Peralta, E., Hanson, E., Marcusson, E.G., Ravichandran, L.V., Sun, Y., Koo, S., Perera, R.J., Jain, R., et al. (2004). MicroRNA-143 regulates adipocyte differentiation. The Journal of biological chemistry 279, 52361-52365. Eulalio, A., Behm-Ansmant, I., and Izaurralde, E. (2007). P bodies: at the crossroads of post-transcriptional pathways. Nature reviews Molecular cell biology 8, 9-22. Evans, P.M., Chen, X., Zhang, W., and Liu, C. (2010). KLF4 interacts with beta-catenin/TCF4 and blocks p300/CBP recruitment by beta-catenin. Molecular and cellular biology 30, 372-381. Fabian, M.R., Cieplak, M.K., Frank, F., Morita, M., Green, J., Srikumar, T., Nagar, B., Yamamoto, T., Raught, B., Duchaine, T.F., et al. (2011). miRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT. Nature structural & molecular biology 18, 1211-1217. Fabian, M.R., Mathonnet, G., Sundermeier, T., Mathys, H., Zipprich, J.T., Svitkin, Y.V., Rivas, F., Jinek, M., Wohlschlegel, J., Doudna, J.A., et al. (2009). Mammalian miRNA RISC recruits CAF1 and PABP to affect PABP-dependent deadenylation. Molecular cell 35, 868-880. Fadeel, B., Orrenius, S., and Zhivotovsky, B. (1999). Apoptosis in human disease: a new skin for the old ceremony? Biochemical and biophysical research communications 266, 699-717. Favereaux, A., Thoumine, O., Bouali-Benazzouz, R., Roques, V., Papon, M.A., Salam, S.A., Drutel, G., Leger, C., Calas, A., Nagy, F., et al. (2011). Bidirectional integrative regulation of Cav1.2 calcium channel by microRNA miR-103: role in pain. The EMBO journal 30, 3830-3841. Fidler, I.J., Yano, S., Zhang, R.D., Fujimaki, T., and Bucana, C.D. (2002). The seed and soil hypothesis: vascularisation and brain metastases. The lancet oncology 3, 53-57. Finger, E.C., and Giaccia, A.J. (2010). Hypoxia, inflammation, and the tumor microenvironment in metastatic disease. Cancer metastasis reviews 29, 285-293. Finnerty, J.R., Wang, W.X., Hebert, S.S., Wilfred, B.R., Mao, G., and Nelson, P.T. (2010). The miR-15/107 group of microRNA genes: evolutionary biology, cellular functions, and roles in human diseases. Journal of molecular biology 402, 491-509. Gabriely, G., Wurdinger, T., Kesari, S., Esau, C.C., Burchard, J., Linsley, P.S., and Krichevsky, A.M. (2008). MicroRNA 21 promotes glioma invasion by targeting matrix metalloproteinase regulators. Molecular and cellular biology 28, 5369-5380. Garrett-Sinha, L.A., Eberspaecher, H., Seldin, M.F., and de Crombrugghe, B. (1996). A gene for a novel zinc-finger protein expressed in differentiated epithelial cells and transiently in certain mesenchymal cells. The Journal of biological chemistry 271, 31384-31390. Gaur, A., Jewell, D.A., Liang, Y., Ridzon, D., Moore, J.H., Chen, C., Ambros, V.R., and Israel, M.A. (2007). Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer research 67, 2456-2468. Ghaleb, A.M., McConnell, B.B., Kaestner, K.H., and Yang, V.W. (2011). Altered intestinal epithelial homeostasis in mice with intestine-specific deletion of the Kruppel-like factor 4 gene. Developmental biology 349, 310-320. Ghaleb, A.M., McConnell, B.B., Nandan, M.O., Katz, J.P., Kaestner, K.H., and Yang, V.W. (2007). Haploinsufficiency of Kruppel-like factor 4 promotes adenomatous polyposis coli dependent intestinal tumorigenesis. Cancer research 67, 7147-7154. Ghildiyal, M., Xu, J., Seitz, H., Weng, Z., and Zamore, P.D. (2010). Sorting of Drosophila small silencing RNAs partitions microRNA* strands into the RNA interference pathway. RNA 16, 43-56. Gilbert, S., Loranger, A., Daigle, N., and Marceau, N. (2001). Simple epithelium keratins 8 and 18 provide resistance to Fas-mediated apoptosis. The protection occurs through a receptor-targeting modulation. The Journal of cell biology 154, 763-773. Gilbert, S., Ruel, A., Loranger, A., and Marceau, N. (2008). Switch in Fas-activated death signaling pathway as result of keratin 8/18-intermediate filament loss. Apoptosis : an international journal on programmed cell death 13, 1479-1493. Gozuacik, D., and Kimchi, A. (2006). DAPk protein family and cancer. Autophagy 2, 74-79. Gregory, P.A., Bert, A.G., Paterson, E.L., Barry, S.C., Tsykin, A., Farshid, G., Vadas, M.A., Khew-Goodall, Y., and Goodall, G.J. (2008). The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nature cell biology 10, 593-601. Grimson, A., Farh, K.K., Johnston, W.K., Garrett-Engele, P., Lim, L.P., and Bartel, D.P. (2007). MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Molecular cell 27, 91-105. Gu, S., Jin, L., Zhang, F., Sarnow, P., and Kay, M.A. (2009). Biological basis for restriction of microRNA targets to the 3' untranslated region in mammalian mRNAs. Nature structural & molecular biology 16, 144-150. Guo, W., and Giancotti, F.G. (2004). Integrin signalling during tumour progression. Nature reviews Molecular cell biology 5, 816-826. Gupta, G.P., and Massague, J. (2006). Cancer metastasis: building a framework. Cell 127, 679-695. Gupta, P.B., Mani, S., Yang, J., Hartwell, K., and Weinberg, R.A. (2005). The evolving portrait of cancer metastasis. Cold Spring Harbor symposia on quantitative biology 70, 291-297. Hanahan, D., and Folkman, J. (1996). Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86, 353-364. Hanahan, D., and Weinberg, R.A. (2000). The hallmarks of cancer. Cell 100, 57-70. Hanahan, D., and Weinberg, R.A. (2011). Hallmarks of cancer: the next generation. Cell 144, 646-674. Hazan, R.B., Qiao, R., Keren, R., Badano, I., and Suyama, K. (2004). Cadherin switch in tumor progression. Annals of the New York Academy of Sciences 1014, 155-163. He, L., and Hannon, G.J. (2004). MicroRNAs: small RNAs with a big role in gene regulation. Nature reviews Genetics 5, 522-531. Hedberg, K.K., and Chen, L.B. (1986). Absence of intermediate filaments in a human adrenal cortex carcinoma-derived cell line. Experimental cell research 163, 509-517. Hengartner, M.O. (2000). The biochemistry of apoptosis. Nature 407, 770-776. Hinnebusch, A.G. (2006). eIF3: a versatile scaffold for translation initiation complexes. Trends in biochemical sciences 31, 553-562. Hurteau, G.J., Carlson, J.A., Spivack, S.D., and Brock, G.J. (2007). Overexpression of the microRNA hsa-miR-200c leads to reduced expression of transcription factor 8 and increased expression of E-cadherin. Cancer research 67, 7972-7976. Hynes, R.O. (2002). Integrins: bidirectional, allosteric signaling machines. Cell 110, 673-687. Ide, T., Kitajima, Y., Miyoshi, A., Ohtsuka, T., Mitsuno, M., Ohtaka, K., Koga, Y., and Miyazaki, K. (2006). Tumor-stromal cell interaction under hypoxia increases the invasiveness of pancreatic cancer cells through the hepatocyte growth factor/c-Met pathway. International journal of cancer Journal international du cancer 119, 2750-2759. Imai, T., Horiuchi, A., Wang, C., Oka, K., Ohira, S., Nikaido, T., and Konishi, I. (2003). Hypoxia attenuates the expression of E-cadherin via up-regulation of SNAIL in ovarian carcinoma cells. The American journal of pathology 163, 1437-1447. Inada, H., Izawa, I., Nishizawa, M., Fujita, E., Kiyono, T., Takahashi, T., Momoi, T., and Inagaki, M. (2001). Keratin attenuates tumor necrosis factor-induced cytotoxicity through association with TRADD. The Journal of cell biology 155, 415-426. Inbal, B., Cohen, O., Polak-Charcon, S., Kopolovic, J., Vadai, E., Eisenbach, L., and Kimchi, A. (1997). DAP kinase links the control of apoptosis to metastasis. Nature 390, 180-184. Inbal, B., Shani, G., Cohen, O., Kissil, J.L., and Kimchi, A. (2000). Death-associated protein kinase-related protein 1, a novel serine/threonine kinase involved in apoptosis. Molecular and cellular biology 20, 1044-1054. Jaakkola, P., Mole, D.R., Tian, Y.M., Wilson, M.I., Gielbert, J., Gaskell, S.J., Kriegsheim, A., Hebestreit, H.F., Mukherji, M., Schofield, C.J., et al. (2001). Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292, 468-472. Jenkins, T.D., Opitz, O.G., Okano, J., and Rustgi, A.K. (1998). Transactivation of the human keratin 4 and Epstein-Barr virus ED-L2 promoters by gut-enriched Kruppel-like factor. The Journal of biological chemistry 273, 10747-10754. Jiang, J., Chan, Y.S., Loh, Y.H., Cai, J., Tong, G.Q., Lim, C.A., Robson, P., Zhong, S., and Ng, H.H. (2008). A core Klf circuitry regulates self-renewal of embryonic stem cells. Nature cell biology 10, 353-360. John, B., Enright, A.J., Aravin, A., Tuschl, T., Sander, C., and Marks, D.S. (2004). Human MicroRNA targets. PLoS biology 2, e363. Joyce, J.A. (2005). Therapeutic targeting of the tumor microenvironment. Cancer cell 7, 513-520. Kallio, P.J., Okamoto, K., O'Brien, S., Carrero, P., Makino, Y., Tanaka, H., and Poellinger, L. (1998). Signal transduction in hypoxic cells: inducible nuclear translocation and recruitment of the CBP/p300 coactivator by the hypoxia-inducible factor-1alpha. The EMBO journal 17, 6573-6586. Kang, Y., and Massague, J. (2004). Epithelial-mesenchymal transitions: twist in development and metastasis. Cell 118, 277-279. Katz, J.P., Perreault, N., Goldstein, B.G., Actman, L., McNally, S.R., Silberg, D.G., Furth, E.E., and Kaestner, K.H. (2005). Loss of Klf4 in mice causes altered proliferation and differentiation and precancerous changes in the adult stomach. Gastroenterology 128, 935-945. Kerr, J.F., Wyllie, A.H., and Currie, A.R. (1972). Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. British journal of cancer 26, 239-257. Kim, J.W., Wong, C.W., Goldsmith, J.D., Song, C., Fu, W., Allion, M.B., Herlyn, M., Al-Mehdi, A.B., and Muschel, R.J. (2004). Rapid apoptosis in the pulmonary vasculature distinguishes non-metastatic from metastatic melanoma cells. Cancer letters 213, 203-212. Kim, S., and Coulombe, P.A. (2007). Intermediate filament scaffolds fulfill mechanical, organizational, and signaling functions in the cytoplasm. Genes & development 21, 1581-1597. Kim, V.N. (2005). MicroRNA biogenesis: coordinated cropping and dicing. Nature reviews Molecular cell biology 6, 376-385. Kiriakidou, M., Tan, G.S., Lamprinaki, S., De Planell-Saguer, M., Nelson, P.T., and Mourelatos, Z. (2007). An mRNA m7G cap binding-like motif within human Ago2 represses translation. Cell 129, 1141-1151. Kischkel, F.C., Hellbardt, S., Behrmann, I., Germer, M., Pawlita, M., Krammer, P.H., and Peter, M.E. (1995). Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. The EMBO journal 14, 5579-5588. Kissil, J.L., Feinstein, E., Cohen, O., Jones, P.A., Tsai, Y.C., Knowles, M.A., Eydmann, M.E., and Kimchi, A. (1997). DAP-kinase loss of expression in various carcinoma and B-cell lymphoma cell lines: possible implications for role as tumor suppressor gene. Oncogene 15, 403-407. Kopfstein, L., and Christofori, G. (2006). Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment. Cellular and molecular life sciences : CMLS 63, 449-468. Korpal, M., Lee, E.S., Hu, G., and Kang, Y. (2008). The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. The Journal of biological chemistry 283, 14910-14914. Krishnamachary, B., Berg-Dixon, S., Kelly, B., Agani, F., Feldser, D., Ferreira, G., Iyer, N., LaRusch, J., Pak, B., Taghavi, P., et al. (2003). Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1. Cancer research 63, 1138-1143. Krishnamachary, B., Zagzag, D., Nagasawa, H., Rainey, K., Okuyama, H., Baek, J.H., and Semenza, G.L. (2006). Hypoxia-inducible factor-1-dependent repression of E-cadherin in von Hippel-Lindau tumor suppressor-null renal cell carcinoma mediated by TCF3, ZFHX1A, and ZFHX1B. Cancer research 66, 2725-2731. Krol, J., Loedige, I., and Filipowicz, W. (2010). The widespread regulation of microRNA biogenesis, function and decay. Nature reviews Genetics 11, 597-610. Ku, N.O., Gish, R., Wright, T.L., and Omary, M.B. (2001). Keratin 8 mutations in patients with cryptogenic liver disease. The New England journal of medicine 344, 1580-1587. Ku, N.O., Liao, J., and Omary, M.B. (1997a). Apoptosis generates stable fragments of human type I keratins. The Journal of biological chemistry 272, 33197-33203. Ku, N.O., and Omary, M.B. (2001). Effect of mutation and phosphorylation of type I keratins on their caspase-mediated degradation. The Journal of biological chemistry 276, 26792-26798. Ku, N.O., and Omary, M.B. (2006). A disease- and phosphorylation-related nonmechanical function for keratin 8. The Journal of cell biology 174, 115-125. Ku, N.O., Toivola, D.M., Strnad, P., and Omary, M.B. (2010). Cytoskeletal keratin glycosylation protects epithelial tissue from injury. Nature cell biology 12, 876-885. Ku, N.O., Wright, T.L., Terrault, N.A., Gish, R., and Omary, M.B. (1997b). Mutation of human keratin 18 in association with cryptogenic cirrhosis. The Journal of clinical investigation 99, 19-23. Kulshreshtha, R., Ferracin, M., Wojcik, S.E., Garzon, R., Alder, H., Agosto-Perez, F.J., Davuluri, R., Liu, C.G., Croce, C.M., Negrini, M., et al. (2007). A microRNA signature of hypoxia. Molecular and cellular biology 27, 1859-1867. Kuo, J.C., Wang, W.J., Yao, C.C., Wu, P.R., and Chen, R.H. (2006). The tumor suppressor DAPK inhibits cell motility by blocking the integrin-mediated polarity pathway. The Journal of cell biology 172, 619-631. Kuo, T.H., Kubota, T., Watanabe, M., Furukawa, T., Teramoto, T., Ishibiki, K., Kitajima, M., Moossa, A.R., Penman, S., and Hoffman, R.M. (1995). Liver colonization competence governs colon cancer metastasis. Proceedings of the National Academy of Sciences of the United States of America 92, 12085-12089. Leber, M.F., and Efferth, T. (2009). Molecular principles of cancer invasion and metastasis (review). International journal of oncology 34, 881-895. Lee, J.C., Schickling, O., Stegh, A.H., Oshima, R.G., Dinsdale, D., Cohen, G.M., and Peter, M.E. (2002). DEDD regulates degradation of intermediate filaments during apoptosis. The Journal of cell biology 158, 1051-1066. Leers, M.P., Kolgen, W., Bjorklund, V., Bergman, T., Tribbick, G., Persson, B., Bjorklund, P., Ramaekers, F.C., Bjorklund, B., Nap, M., et al. (1999). Immunocytochemical detection and mapping of a cytokeratin 18 neo-epitope exposed during early apoptosis. The Journal of pathology 187, 567-572. Lehmann, U., Celikkaya, G., Hasemeier, B., Langer, F., and Kreipe, H. (2002). Promoter hypermethylation of the death-associated protein kinase gene in breast cancer is associated with the invasive lobular subtype. Cancer research 62, 6634-6638. Leslie, N.R., Yang, X., Downes, C.P., and Weijer, C.J. (2005). The regulation of cell migration by PTEN. Biochemical Society transactions 33, 1507-1508. Lewis, B.P., Burge, C.B., and Bartel, D.P. (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15-20. Li, D., Peng, Z., Tang, H., Wei, P., Kong, X., Yan, D., Huang, F., Li, Q., Le, X., and Xie, K. (2011). KLF4-mediated negative regulation of IFITM3 expression plays a critical role in colon cancer pathogenesis. Clinical cancer research : an official journal of the American Association for Cancer Research 17, 3558-3568. Li, H., Zhu, H., Xu, C.J., and Yuan, J. (1998). Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94, 491-501. Li, J., Huang, H., Sun, L., Yang, M., Pan, C., Chen, W., Wu, D., Lin, Z., Zeng, C., Yao, Y., et al. (2009). MiR-21 indicates poor prognosis in tongue squamous cell carcinomas as an apoptosis inhibitor. Clinical cancer research : an official journal of the American Association for Cancer Research 15, 3998-4008. Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S.M., Ahmad, M., Alnemri, E.S., and Wang, X. (1997). Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91, 479-489. Li, R., Liang, J., Ni, S., Zhou, T., Qing, X., Li, H., He, W., Chen, J., Li, F., Zhuang, Q., et al. (2010). A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts. Cell stem cell 7, 51-63. Liu, J., Valencia-Sanchez, M.A., Hannon, G.J., and Parker, R. (2005). MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nature cell biology 7, 719-723. Liu, Y.L., Yu, J.M., Song, X.R., Wang, X.W., Xing, L.G., and Gao, B.B. (2006). Regulation of the chemokine receptor CXCR4 and metastasis by hypoxia-inducible factor in non small cell lung cancer cell lines. Cancer biology & therapy 5, 1320-1326. Long, D., Lee, R., Williams, P., Chan, C.Y., Ambros, V., and Ding, Y. (2007). Potent effect of target structure on microRNA function. Nature structural & molecular biology 14, 287-294. Lowthert, L.A., Ku, N.O., Liao, J., Coulombe, P.A., and Omary, M.B. (1995). Empigen BB: a useful detergent for solubilization and biochemical analysis of keratins. Biochemical and biophysical research communications 206, 370-379. Lu, X., and Kang, Y. (2010). Hypoxia and hypoxia-inducible factors: master regulators of metastasis. Clinical cancer research : an official journal of the American Association for Cancer Research 16, 5928-5935. Lu, X., Yan, C.H., Yuan, M., Wei, Y., Hu, G., and Kang, Y. (2010). In vivo dynamics and distinct functions of hypoxia in primary tumor growth and organotropic metastasis of breast cancer. Cancer research 70, 3905-3914. Luo, J., Dunn, T., Ewing, C., Sauvageot, J., Chen, Y., Trent, J., and Isaacs, W. (2002). Gene expression signature of benign prostatic hyperplasia revealed by cDNA microarray analysis. The Prostate 51, 189-200. Luo, X., Budihardjo, I., Zou, H., Slaughter, C., and Wang, X. (1998). Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 94, 481-490. Lytle, J.R., Yario, T.A., and Steitz, J.A. (2007). Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5' UTR as in the 3' UTR. Proceedings of the National Academy of Sciences of the United States of America 104, 9667-9672. Ma, L., Teruya-Feldstein, J., and Weinberg, R.A. (2007). Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449, 682-688. Madden, S.L., Cook, B.P., Nacht, M., Weber, W.D., Callahan, M.R., Jiang, Y., Dufault, M.R., Zhang, X., Zhang, W., Walter-Yohrling, J., et al. (2004). Vascular gene expression in nonneoplastic and malignant brain. The American journal of pathology 165, 601-608. Magin, T.M., Vijayaraj, P., and Leube, R.E. (2007). Structural and regulatory functions of keratins. Experimental cell research 313, 2021-2032. Mandanas, R.A., Leibowitz, D.S., Gharehbaghi, K., Tauchi, T., Burgess, G.S., Miyazawa, K., Jayaram, H.N., and Boswell, H.S. (1993). Role of p21 RAS in p210 bcr-abl transformation of murine myeloid cells. Blood 82, 1838-1847. Martello, G., Rosato, A., Ferrari, F., Manfrin, A., Cordenonsi, M., Dupont, S., Enzo, E., Guzzardo, V., Rondina, M., Spruce, T., et al. (2010). A MicroRNA targeting dicer for metastasis control. Cell 141, 1195-1207. Masutani, M., Sonenberg, N., Yokoyama, S., and Imataka, H. (2007). Reconstitution reveals the functional core of mammalian eIF3. The EMBO journal 26, 3373-3383. Mayeur, G.L., Fraser, C.S., Peiretti, F., Block, K.L., and Hershey, J.W. (2003). Characterization of eIF3k: a newly discovered subunit of mammalian translation initiation factor elF3. European journal of biochemistry / FEBS 270, 4133-4139. McLean, G.W., Carragher, N.O., Avizienyte, E., Evans, J., Brunton, V.G., and Frame, M.C. (2005). The role of focal-adhesion kinase in cancer - a new therapeutic opportunity. Nature reviews Cancer 5, 505-515. Micheau, O., and Tschopp, J. (2003). Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 114, 181-190. Minn, A.J., Kang, Y., Serganova, I., Gupta, G.P., Giri, D.D., Doubrovin, M., Ponomarev, V., Gerald, W.L., Blasberg, R., and Massague, J. (2005). Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors. The Journal of clinical investigation 115, 44-55. Miramar, M.D., Costantini, P., Ravagnan, L., Saraiva, L.M., Haouzi, D., Brothers, G., Penninger, J.M., Peleato, M.L., Kroemer, G., and Susin, S.A. (2001). NADH oxidase activity of mitochondrial apoptosis-inducing factor. The Jour | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/66513 | - |
dc.description.abstract | 迴避死亡及癌細胞組織浸潤轉移是癌症的兩大特徵,在我論文的第一個部
份,主要是針對一種抑制癌症的細胞死亡形式—細胞凋亡的機探討,我們發現真 核轉譯起始因子 3k (eIF3k) 在表皮細胞中具有調控細胞凋亡的角色。eIF3k 已知 為 eIF3 複合體中的一個次單位,除此之外,在我們的研究中發現 eIF3k 會表現 於角質中間絲細胞骨架(keratin intermediate filaments)上,並與 18 號細胞角質 蛋白(K18)作結合,一旦啟動細胞凋亡的機制,eIF3k 會藉由與 keratin的作用進 入含有 K8 及 K18 的包含體中。先前已知這些含有 K8 及 K18 之包含體具有延 緩細胞凋亡進行的功能,可以擒住一部份的半胱氨酸蛋白(caspases),降低其與 受質接觸的機率,進而延緩細胞凋亡之進行。本研究發現 eIF3k 藉使 caspases 自 包含體釋放出來,進而促進細胞凋亡的進行。因此,本研究發現因此,本研究發 現 eIF3k 在細胞中不僅會與 eIF3 複合體結合,亦會與 keratin 結合,展現其不 同於 eIF3 複合體之特性,並藉由此種交互作用執行其特殊之生理功能,進而調控 細胞凋亡之進行。 接下來,在我論文的第二部份,主要是針對在結直腸癌 (CRC) 中,微型核糖 核酸 (microRNA) 對腫瘤轉移的調控機制探討,我們發現微型核糖核酸 103 號及 107 號 (miR-103/107) 具有促進腫瘤轉移的功能。首先,在一系列結直腸癌細胞 株中,我們發現 miR-103/107 的表現量與各細胞株的轉移潛能有正相關的現象, 且 miR-103/107 促進細胞移動能力,促進細胞與基質的黏附以及抑制細胞與細胞 之間的黏附等,在在皆顯示出 miR-103/107 可促進各種腫瘤轉移相關的特性,且 這些特性也被發現是透過抑制死亡相關蛋白激酶 (DAPK) 及 Krüppel 樣因子4 (KLF4) 所達成的。更重要的是,在缺氧情況下能促進細胞移動轉移的現象這條訊 息途逕也參予其中。最後,我們利用原位 CRC 腫瘤模型,再次應證了 miR-103/107 可透過抑制 DAPK 及 KLF4 的交互作用而達到促進 CRC 之腫瘤轉移。 總結,我們的研究發現了 eIF3k 具有調控細胞凋亡的功能以及探討了 miR-103/107 對腫瘤轉移的影響,期望對於腫瘤進程的研究能帶來幫助。 | zh_TW |
dc.description.abstract | Resistance to cell death and activation of invasion-metastasis cascade are two of the
hallmarks of cancer. In the first part of this thesis, I focus on the molecular mechanism of apoptosis, a form of cell death that has profound impacts on tumor suppression. I identify eIF3k as a novel regulator of apoptosis in simple epithelial cells. Despite being identified as a component of the eIF3 complex, a large portion of eIF3k is present in the keratin 8 and 18 (collectively called K8/K18) intermediate filaments through its physical association with K18. Upon induction of apoptosis, eIF3k colocalizes with K8/K18 in the cytoplasmic inclusions. Depletion of eIF3k de-sensitizes simple epithelial cells to various types of apoptosis through a K8/K18-dependent manner. Mechanistically, this attenuation of apoptosis is due to the retention of active caspase 3 in K8/K18-containing cytoplasmic inclusions by increasing its binding to keratins. Consequently, the cleavage of caspase cytosolic and nuclear substrates, such as ICAD and PARP, respectively, is reduced in eIF3k-depleted cells. Hence, this study identifies an apoptosis-promoting function of eIF3k in simple epithelial cells by relieving the caspase-sequestration effect of K8/K18, thereby increasing the availability of caspases to their non-keratin-residing substrates. The aim of the second part of this thesis is to unravel the function of microRNAs (miRNAs) in metastasis process of colorectal cancer (CRC). I identify miR-103 and miR-107 (miR-103/107) as potential metastamirs in CRC. First, miR-103/107 expression correlates with metastatic potential of CRC cell line. Second, miR-103/107 protentiate a number of metastasis-relevant traits in vitro, such as increasing motility and cell-matrix adhesion and suppressing cell-cell contact assembly. These functions are mediated at least in part by the repression of two metastasis suppressors, death-associated protein kinase (DAPK) and Krüppel-like factor 4 (KLF4). Importantly, miR-103-1 and miR-107 are transcriptional targets of HIF-1 and their repression of DAPK and KLF4 mediates hypoxia-induced migration and invasion. In orthotopic CRC model, overexpression of miR-103/107 potentiates CRC metastasis and this effect is blocked by re-expression of DAPK or KLF4. These data indicate that miR-103/107 coordinately repress DAPK and KLF4 to potentiate CRC metastasis and this regulatory scheme contributes in part to hypoxia-stimulated tumor metastasis. In conclusion, the uncovering of eIF3k apoptotic function and miR-103/107 metastatic effect would shed light on the tumor progression mechanism. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T00:39:56Z (GMT). No. of bitstreams: 1 ntu-101-D95b46009-1.pdf: 6604276 bytes, checksum: 70520e75c0285a463dce86fdb9abc014 (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | Table contents
Abbreviations .................................................................................................................... i 中文摘要.......................................................................................................................... ii Abstract........................................................................................................................... iii Literature Review ............................................................................................................. 1 1. Tumor progression............................................................................................ 1 1.1 Six acquired hallmarks in tumor progression................................... 1 1.1.1 Self-sufficiency in growth signals ............................................ 1 1.1.2 Sustained angiogenesis.............................................................1 1.1.3 Insensitivity to growth-inhibitor signals................................... 2 1.1.4 Evasion of apoptosis................................................................. 2 1.1.5 Limitless replicative potential .................................................. 2 1.1.6 Tissue invasion and metastasis ................................................. 2 1.2 Two enabling hallmarks in tumor progression ................................. 3 1.3 Apoptosis..........................................................................................4 1.3.1 Morphological features of apoptosis ........................................ 4 1.3.2 Caspases, the central initiators and executioners of apoptosis . 4 1.3.3 Molecular mechanisms of apoptosis signaling pathways......... 5 1.3.3.1 Intrinsic pathway .............................................................. 5 1.3.3.2 Extrinsic pathway ............................................................. 5 1.3.3.3 Crosstalk between two pathways...................................... 6 1.4 Metastasis .........................................................................................7 1.4.1 Metastasis cascade: invasion and migration............................. 7 1.4.2 Metastasis cascade: intravasation, circulation and arrest ......... 8 1.4.3 Metastasis cascade: extravasation and colonization................. 8 1.5 Hypoxia ............................................................................................9 1.5.1 Hypoxia-induced biological events .......................................... 9 1.5.1.1 EMT.................................................................................. 9 1.5.1.2 ECM modulation .............................................................. 9 1.5.1.3 Receptor-ligand signaling................................................. 9 1.5.1.4 VEGF production ........................................................... 10 1.5.1.5 Homing ........................................................................... 10 1.5.2 Hypoxia-inducible factors (HIFs)........................................... 10 2. Keratin intermediate filaments ........................................................................11 2.1 Keratin intermediate filaments and apoptosis .................................11 2.1.1 Simple epithelial keratins as targets in apoptosis ................... 12 2.1.2 K8/K18 as modulators of apoptosis ....................................... 13 3. microRNAs..................................................................................................... 14 3.1 microRNA biogenesis and function................................................ 14 3.2 The role of microRNAs in metastasis ............................................ 16 3.3 The role of miR-103/107 in tumor progression.............................. 17 4. Eukaryotic translation initiation factor 3k (eIF3k) ......................................... 18 5. Death-associated protein kinase (DAPK)....................................................... 18 5.1 The role of DAPK in tumorigenesis............................................... 19 6. Krüppel-like factor 4 (KLF4) ......................................................................... 20 6.1 Krüppel-like factor family .............................................................. 20 6.2 The physiological role KLF4.......................................................... 21 6.3 The role of KLF4 in tumorigenesis ................................................ 22 Chapter I ......................................................................................................................... 24 eIF3k regulates apoptosis in epithelial cells by releasing caspase 3 from keratin-containing inclusions.......................................................................................... 24 Abstract.......................................................................................................................... 25 Introduction .................................................................................................................... 26 Results ............................................................................................................................ 28 Characterization of the eIF3k antiserum ................................................................ 28 eIF3k colocalizes with K8/K18 filaments .............................................................. 28 eIF3k associates with K18...................................................................................... 30 Down-regulation of eIF3k attenuates apoptosis ..................................................... 30 eIF3k colocalizes with K8/K18 in the cytoplasmic inclusions in apoptotic cells .. 31 K8/K18 are required for the apoptosis-promoting function of eIF3k .................... 32 eIF3k promotes the release of active caspase 3 from K8/K18-residing insoluble inclusions................................................................................................................ 32 eIF3k decreases K8/K18-associated caspase 3 and increases availability of caspase 3 to non-keratin-residing substrates........................................................................ 34 Discussion...................................................................................................................... 35 Materials and Methods ................................................................................................... 37 Cloning of eIF3k and generation of antiserum to eIF3k ........................................ 37 Plasmid construction .............................................................................................. 37 Cell culture and transfection................................................................................... 38 Apoptosis induction and assay ............................................................................... 38 Western blot and antibodies.................................................................................... 39 Immunofluorescence and confocal studies............................................................. 39 Yeast two-hybrid assay ........................................................................................... 40 Immunoprecipitations............................................................................................. 40 Detergent extraction for separating soluble and insoluble proteins ....................... 40 Calculation of the percentage of eIF3k associated with K18 in vivo..................... 41 Chapter II........................................................................................................................ 42 miR-103/107 target DAPK and KLF4 to promote colon cancer metastasis .................. 42 Abstract.......................................................................................................................... 43 Introduction .................................................................................................................... 44 Results ............................................................................................................................ 45 miR-103/107 are up-regulated in highly metastatic CRC cell lines....................... 45 miR-103/107 promote metastasis-relevant traits in vitro ....................................... 46 miR-103/107 target DAPK and KLF4.................................................................... 47 Re-expression of DAPK and KLF4 override miR-103/107-induced metastasis-relevant phenotypes in vitro.................................................................. 48 miR-103/107 are transcriptional targets in HIF-1 .................................................. 48 miR-103/107-mediated repression of DAPK and KLF4 contributes to hypoxia-induced migration and invasion. .............................................................. 49 Re-expression of DAPK and KLF4 reverses miR-103/107-imposed metastasis in vivo. ........................................................................................................................ 49 Discussion...................................................................................................................... 50 Materials and Methods ................................................................................................... 52 Plasmids.................................................................................................................. 52 Cell culture and transfection................................................................................... 53 Antibodies and reagents.......................................................................................... 53 Lentivirus production and infection ....................................................................... 53 RNAi interference .................................................................................................. 54 Flow cytometry analysis of integrin expression..................................................... 54 ChIP assay .............................................................................................................. 54 Real-time RT-PCR assay for mature miRNA and mRNA expression.................... 55 Cell adhesion assay................................................................................................. 56 Calcium switch experiment .................................................................................... 56 Cell migration and invasion assay.......................................................................... 56 In vivo models ........................................................................................................ 56 Figure............................................................................................................................. 58 Fig. 1. Characterization of the eIF3k antiserum. .................................................... 58 Fig. 2. Characterization of the subcellular distribution of eIF3k. .......................... 59 Fig. 3. Validation of the specificity of the eIF3k antibody in immunostaining analyses................................................................................................................... 60 Fig. 4. Distribution of eIF3k in both the detergent-soluble and -insoluble compartments of cells............................................................................................. 61 Fig. 5. Distributions of eIF3k and K8 in various tissues. ....................................... 62 Fig. 6. Calculation of the percentage of eIF3k associated with K18 in vivo. ........ 63 Fig. 7. Mapping the domains responsible for the interaction of eIF3k with K18. . 64 Fig. 8. eIF3k does not affect the integrity and organization of K8/K18 filaments. 65 Fig. 9. Down-regulation of eIF3k protects cells from apoptosis............................ 66 Fig. 10. Clonogenic survival of UV irradiated cells carrying eIF3k siRNA or control siRNA......................................................................................................... 67 Fig. 11. Expression of the siRNA-resistant eIF3k (eIF3kr) construct reverses the apoptosis modulating effect of eIF3k siRNA. ........................................................ 68 Fig.12. Colocalization of eIF3k and K8/K18 in cytoplasmic inclusions of apoptotic cells......................................................................................................................... 69 Fig. 13. The formation of cytoplasmic inclusions and localization of eIF3k in these inclusions are both dependent on caspase activity.................................................. 70 Fig. 14. Colocalization of eIF3k with K18 in cytoplasmic inclusions in various apoptotic systems.................................................................................................... 71 Fig. 15. Down-regulation of eIF3k does not protect SW13 cells from apoptosis. . 72 Fig. 16. eIF3k regulates apoptosis in a K8/K18-dependent manner....................... 73 Fig. 17. Knockdown of eIF3k promotes keratin-dependent sequestration of active caspase 3 in the insoluble compartment of cells..................................................... 74 Fig. 18. Down-regulation of eIF3k promotes the sequestration of active caspase 3 in K8/K18-residing cytoplasmic inclusions. .......................................................... 75 Fig. 19. Interaction of active caspase 3 with K18. ................................................. 76 Fig. 20. Down-regulation of eIF3k increases the association of active caspase 3 with K18 in HeLa cells........................................................................................... 77 Fig. 21. Down-regulation of eIF3k increases the association of active caspase 3 with K18 in SW13-K8/K18 cells. .......................................................................... 78 Fig. 22. The effect of eIF3k on the cleavage of caspase 3 nuclear and cytosolic... 79 substrates. ............................................................................................................... 79 Fig. 23. Model of eIF3k function during apoptosis................................................ 80 Fig. 24. The distribution of overexpressed eIF3k................................................... 81 Fig. 25. The specificity of qPCR primers for monitoring miR-103 and miR-107 expression and the expression of miR-103 and miR-107 in various CRC cell lines. ............................................................................................................................... 82 Fig. 26. The expression of miR-10a, miR-155, miR-210 and miR-486 in various 83 CRC cell lines......................................................................................................... 83 Fig. 27. miR-103 and miR-107 promote migration and invasion in vitro.............. 84 Fig. 28. miR-103/107 cannot induce EMT in CRC cells. ...................................... 85 Fig. 29. miR-103/107 delay cell-cell adhesion....................................................... 86 Fig. 30. miR-103/107 promote migration preferentially on low matrix concentrations......................................................................................................... 87 Fig. 31. miR-103/107 target DAPK and KLF4 by Western blot. ........................... 88 Fig. 32. Re-expression of DAPK blocks miR-103/107-stimulated integrin β1 activity in vitro. ...................................................................................................... 89 Fig. 33. miR-103/107 inhibit the expression of epithelial markers through KLF4 down-regulation...................................................................................................... 90 Fig. 34. miR-103/107 fail to affect the expression of Slug and Snail. ................... 91 Fig. 35. miR-103/107 target DAPK and KLF4 by reporter assays. ....................... 92 Fig. 36. Re-expression of DAPK or KLF4 blocks miR-103/107-induced migration and invasion in vitro. .............................................................................................. 93 Fig. 37. Schematic representation of the promoter regions and reporter constructs used in this study..................................................................................................... 94 Fig. 38. miR-103-1 is a transcriptional target of HIF-1.......................................... 95 Fig. 39. miR-107 is a transcriptional target of HIF-1 by reporter assays. .............. 96 Fig. 40. miR-103-1 and miR-107 are transcriptional targets of HIF-1 by ChIP assays...................................................................................................................... 97 Fig. 41. miR-103/107 participate in hypoxia-induced down-regulation of DAPK and KLF4................................................................................................................ 98 Fig. 42. miR-103/107 mediate hypoxia-induced migration/invasion by repressing DAPK and KLF4.................................................................................................... 99 Appendix ...................................................................................................................... 100 Appendix I. Interaction of eIF3k with K18. ......................................................... 100 Appendix II. miR-103/107 promote cell-matrix adhesion. .................................. 101 Appendix III. Hypoxia induces the expression of miR-103-1 and miR-107 but not miR-103-2............................................................................................................. 102 Appendix IV. miR-103/107 inhibit cell-matrix adhesion through DAPK down-regulation.................................................................................................... 103 Appendix V. miR-103/107-dependent regulation of DAPK and KLF4 potentiates CRC local invasion and metastasis in orthotopic mouse model........................... 104 Appendix VI. Reporter analysis for examining the efficacies of miR-103 and miR-107 and their antagomirs. ............................................................................. 105 Reference...................................................................................................................... 106 | |
dc.language.iso | zh-TW | |
dc.title | eIF3k 及 miR-103/107 在癌症相關特性上之功能探討 | zh_TW |
dc.title | Functional characterization of eIF3k and miR-103/107 in tumor-relevant traits | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-1 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 李芳仁,張久瑗,周玉山,陳光超 | |
dc.subject.keyword | 真核轉譯因子3k,Kr&uuml,ppel 樣因子4,細胞凋亡,腫瘤轉移, | zh_TW |
dc.subject.keyword | eIF3k,KLF4,apoptosis,metastasis, | en |
dc.relation.page | 123 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2012-01-19 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生化科學研究所 | zh_TW |
顯示於系所單位: | 生化科學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-101-1.pdf 目前未授權公開取用 | 6.45 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。