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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 宋麗英(Li-Ying Sung) | |
dc.contributor.advisor | 宋麗英(Li-Ying Sung | liyingsung@ntu.edu.tw | ), | |
dc.contributor.author | Tz-Wei Huang | en |
dc.contributor.author | 黃子瑋 | zh_TW |
dc.date.accessioned | 2023-03-19T23:46:26Z | - |
dc.date.copyright | 2022-09-05 | |
dc.date.issued | 2022 | |
dc.date.submitted | 2022-08-29 | |
dc.identifier.citation | Akhurst, R. J., and Hata, A. (2012). Targeting the TGFβ signaling pathway in disease. Nat. Rev. Drug Discov. 11, 790–811. Allison, K. H., Kandalaft, P. L., Sitlani, C. M., Dintzis, S. M., and Gown, A. M. (2012). Routine pathologic parameters can predict Oncotype DXTM recurrence scores in subsets of ER positive patients: Who does not always need testing? Breast Cancer Res. Treat. 131, 413–424. Aloia, A., Petrova, E., Tomiuk, S., Bissels, U., Déas, O., Saini, M., Zickgraf, F. M., Wagner, S., Spaich, S., Sütterlin, M., et al. (2015). The sialyl-glycolipid stage-specific embryonic antigen 4 marks a subpopulation of chemotherapy-resistant breast cancer cells with mesenchymal features. Breast Cancer Res. 17, 1–17. Bhushan, A., Gonsalves, A., and Menon, J. U. (2021). Current state of breast cancer diagnosis, treatment, and theranostics. Pharmaceutics 13, 723. Birchmeier, C., Birchmeier, W., and Brand-Saberi, B. (1996). Epithelial-mesenchymal transitions in cancer progression. Cells Tissues Organs 156, 217–226. Brennan, K., Offiah, G., McSherry, E. A., and Hopkins, A. M. (2010). Tight junctions: A barrier to the initiation and progression of breast cancer? J. Biomed. Biotech nol. 2010. Chaffer, C. L., San Juan, B. P., Lim, E., and Weinberg, R. A. (2016). EMT, cell plasticity and metastasis. Cancer Metastasis Rev. 35, 645–654. Chang, W. W., Chien, H. L., Lee, P., Lin, J., Hsu, C. W., Hung, J. T., Lin, J. J., Yu, J. C., Shao, L. E., Yu, J., et al. (2008). Expression of Globo H and SSEA3 in breast cancer stem cells and the involvement of fucosyl transferases 1 and 2 in Globo H synthesis (Proceedings of the National Academy of Sciences of the United States of America (2008) 105, (11667-11672) DOI: 10.1073/pn. Proc. Natl. Acad. Sci. U. S. A. 105, 17206. Cheung, S. K. C., Chuang, P. K., Huang, H. W., Hwang-Verslues, W. W., Cho, C. H. H., Yang, W. Bin, Shen, C. N., Hsiao, M., Hsu, T. L., Chang, C. F., et al. (2016). Stage-specific embryonic antigen-3 (SSEA-3) and β3GalT5 are cancer specific and significant markers for breast cancer stem cells. Proc. Natl. Acad. Sci. U. S. A. 113, 960–965. Chuang, P. K., Hsiao, M., Hsu, T. L., Chang, C. F., Wu, C. Y., Chen, B. R., Huang, H. W., Liao, K. S., Chen, C. C., Chen, C. L., et al. (2019). Signaling pathway of globo-series glycosphingolipids and β1,3-galactosyltransferase V (β3GalT5) in breast cancer. Proc. Natl. Acad. Sci. U. S. A. 116, 3518–3523. Colditz, G. A., Kaphingst, K. A., Hankinson, S. E., and Rosner, B. (2012). Family history and risk of breast cancer: Nurses’ health study. Breast Cancer Res. Treat. 133, 1097–1104. Cumin, C., Huang, Y. L., Everest-Dass, A., and Jacob, F. (2021). Deciphering the importance of glycosphingolipids on cellular and molecular mechanisms associated with epithelial-to-mesenchymal transition in cancer. Biomolecules 11, 1–19. Danishefsky, S. J., Shue, Y. K., Chang, M. N., and Wong, C. H. (2015). Development of Globo-H Cancer Vaccine. Acc. Chem. Res. 48, 643–652. DeSantis, C. E., Ma, J., Gaudet, M. M., Newman, L. A., Miller, K. D., Goding Sauer, A., Jemal, A., and Siegel, R. L. (2019). Breast cancer statistics, 2019. CA. Cancer J. Clin. 69, 438–451. Duncan, W., and Kerr, G. R. (1976). The curability of breast cancer. Br. Med. J. 2, 781–783. Fabisiewicz, A., and Grzybowska, E. (2017). CTC clusters in cancer progression and metastasis. Med. Oncol. 34, 1–10. Fantozzi, A., and Christofori, G. (2006). Mouse models of breast cancer metastasis. Breast Cancer Res. 8. Fehm, T., Müller, V., Alix-Panabières, C., and Pantel, K. (2008). Micrometastatic spread in breast cancer: Detection, molecular characterization and clinical relevance. Breast Cancer Res. 10, 1–10. Feng, Y., Spezia, M., Huang, S., Yuan, C., Zeng, Z., Zhang, L., Ji, X., Liu, W., Huang, B., Luo, W., et al. (2018). Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis. Genes Dis. 5, 77–106. Gunasinghe, N. P. A. D., Wells, A., Thompson, E. W., and Hugo, H. J. (2012). Mesenchymal-epithelial transition (MET) as a mechanism for metastatic colonisation in breast cancer. Cancer Metastasis Rev. 31, 469–478. Hakomori, S. itiroh (1991). Possible functions of tumor-associated carbohydrate antigens. Curr. Opin. Immunol. 3, 646–653. Hamamura, K., Hotta, H., Murakumo, Y., Shibuya, H., Kondo, Y., and Furukawa, K. (2020). Ssea-3 and 4 are not essential for the induction or properties of mouse ips cells. J. Oral Sci. 62, 393–396. Hanahan, D., and Weinberg, R. A. (2011). Hallmarks of cancer: The next generation. Cell 144, 646–674. Henderson, J. K., Draper, J. S., Baillie, H. S., Fishel, S., Thomson, J. A., Moore, H., and Andrews, P. W. (2002). Preimplantation Human Embryos and Embryonic Stem Cells Show Comparable Expression of Stage‐Specific Embryonic Antigens. Stem Cells 20, 329–337. Hill, C., and Wang, Y. (2020). The importance of epithelial-mesenchymal transition and autophagy in cancer drug resistance. Cancer Drug Resist. 3, 38–47. Ho, M. Y., Yu, A. L., and Yu, J. (2017). Glycosphingolipid dynamics in human embryonic stem cell and cancer: their characterization and biomedical implications. Glycoconj. J. 34, 765–777. Keith, B., and Simon, M.C. (2015). Tumor Angiogenesis. Mol. Basis Cancer Fourth Ed. 358, 2039–2049. Khanna, C., and Hunter, K. (2005). Modeling metastasis in vivo. Carcinogenesis 26, 513–523. Lai, T. Y., Chen, I. J., Lin, R. J., Liao, G. S., Yeo, H. L., Ho, C. L., Wu, J. C., Chang, N. C., Lee, A. C. L., and Yu, A. L. (2019). Fucosyltransferase 1 and 2 play pivotal roles in breast cancer cells. Cell Death Discov. 5. Lee, R. H., Wang, Y. J., Lai, T. Y., Hsu, T. L., Chuang, P. K., Wu, H. C., and Wong, C. H. (2021). Combined Effect of Anti-SSEA4 and Anti-Globo H Antibodies on Breast Cancer Cells. ACS Chem. Biol. 16, 1526–1537. Li, Q., and Mattingly, R. R. (2008). Restoration of E-cadherin cell-cell junctions requires both expression of E-cadherin and suppression of ERK MAP kinase activation in ras-transformed breast epithelial cells. Neoplasia 10, 1444–1458. Liang, Y. J., Kuo, H. H., Lin, C. H., Chen, Y. Y., Yang, B. C., Cheng, Y. Y., Yu, A. L., Khoo, K. H., and Yu, J. (2010). Switching of the core structures of glycosphingolipids from globo- and lacto- to ganglio-series upon human embryonic stem cell differentiation. Proc. Natl. Acad. Sci. U. S. A. 107, 22564–22569. Liao, Y. M., Wang, Y. H., Hung, J. T., Lin, Y. J., Huang, Y. L., Liao, G. S., Hsu, Y. L., Wu, J. C., and Yu, A. L. (2021). High B3GALT5 expression confers poor clinical outcome and contributes to tumor progression and metastasis in breast cancer. Breast Cancer Res. 23, 1–13. Lorusso, G., and Rüegg, C. (2012). New insights into the mechanisms of organ-specific breast cancer metastasis. Semin. Cancer Biol. 22, 226–233. Mao, Y., Keller, E. T., Garfield, D. H., Shen, K., and Wang, J. (2013). Stromal cells in tumor microenvironment and breast cancer. Cancer Metastasis Rev. 32, 303–315. Nathanson, D. A., Gini, B., Mottahedeh, J., Visnyei, K., Koga, T., Gomez, G., Eskin, A., Hwang, K., Wang, J., Masui, K., et al. (2014). Targeted therapy resistance mediated by dynamic regulation of extrachromosomal mutant EGFR DNA. Science (80-. ). 343, 72–76. Neophytou, C. M., Panagi, M., Stylianopoulos, T., and Papageorgis, P. (2021). The role of tumor microenvironment in cancer metastasis: Molecular mechanisms and therapeutic opportunities. Cancers (Basel). 13, 2053. Nieto, M. A., Huang, R. Y. Y. J., Jackson, R. A. A., and Thiery, J. P. P. (2016). Emt: 2016. Cell 166, 21–45. Nik-Zainal, S., Davies, H., Staaf, J., Ramakrishna, M., Glodzik, D., Zou, X., Martincorena, I., Alexandrov, L. B., Martin, S., Wedge, D. C., et al. (2016). Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature 534, 47–54. Nitta, T., Kanoh, H., Inamori, K. I., Suzuki, A., Takahashi, T., and Inokuchi, J. I. (2018). Globo-series glycosphingolipids enhance Toll-like receptor 4-mediated inflammation and play a pathophysiological role in diabetic nephropathy. Glycobiology 29, 260–268. Nounou, M. I., Elamrawy, F., Ahmed, N., Abdelraouf, K., Goda, S., and Syed-Sha-Qhattal, H. (2015). Breast cancer: Conventional diagnosis and treatment modalities and recent patents and technologies supplementary issue: Targeted therapies in breast cancer treatment. Breast Cancer Basic Clin. Res. 9, 17–34. Reis, C. A., Osorio, H., Silva, L., Gomes, C., and David, L. (2010). Alterations in glycosylation as biomarkers for cancer detection. J. Clin. Pathol. 63, 322–329. Ricciardi, M., Zanotto, M., Malpeli, G., Bassi, G., Perbellini, O., Chilosi, M., Bifari, F., and Krampera, M. (2015). Epithelial-to-mesenchymal transition (EMT) induced by inflammatory priming elicits mesenchymal stromal cell-like immune-modulatory properties in cancer cells. Br. J. Cancer 112, 1067–1075. Rodriguez-Monterrosas, C., Díaz-Aragon, R., Leal-Orta, E., Cortes-Reynosa, P., and Perez Salazar, E. (2018). Insulin induces an EMT-like process in mammary epithelial cells MCF10A. J. Cell. Biochem. 119, 4061–4071. Sannino, G., Marchetto, A., Kirchner, T., and Grünewald, T.G.P. (2017). Epithelial-to-mesenchymal and mesenchymal-to-epithelial transition in mesenchymal tumors: A paradox in sarcomas? Cancer Res. 77, 4556–4561. Schmalhofer, O., Brabletz, S., and Brabletz, T. (2009). E-cadherin, β-catenin, and ZEB1 in malignant progression of cancer. Cancer Metastasis Rev. 28, 151–166. Sigal, D. S., Hermel, D. J., Hsu, P., and Pearce, T. (2022). The role of Globo H and SSEA-4 in the development and progression of cancer, and their potential as therapeutic targets. Futur. Oncol. 18, 117–134. Sivasubramaniyan, K., Harichandan, A., Schilbach, K., Mack, A. F., Bedke, J., Stenzl, A., Kanz, L., Niederfellner, G., and Bühring, H. J. (2015). Expression of stage-specific embryonic antigen-4 (SSEA-4) defines spontaneous loss of epithelial phenotype in human solid tumor cells. Glycobiology 25, 902–917. Smith, B. N., and Bhowmick, N. A. (2016). Role of EMT in metastasis and therapy resistance. J. Clin. Med. 5, 1–17. Sulaiman, A., Yao, Z., and Wang, L. (2018). Re-evaluating the role of epithelial-mesenchymal-transition in cancer progression. J. Biomed. Res. 32, 81–90. Sun, Y. S., Zhao, Z., Yang, Z. N., Xu, F., Lu, H. J., Zhu, Z. Y., Shi, W., Jiang, J., Yao, P. P., and Zhu, H. P. (2017). Risk factors and preventions of breast cancer. Int. J. Biol. Sci. 13, 1387–1397. Tam, W. L., and Weinberg, R. A. (2013). The epigenetics of epithelial-mesenchymal plasticity in cancer. Nat. Med. 19, 1438–1449. Theys, J., Jutten, B., Habets, R., Paesmans, K., Groot, A. J., Lambin, P., Wouters, B. G., Lammering, G., and Vooijs, M. (2011). E-Cadherin loss associated with EMT promotes radioresistance in human tumor cells. Radiother. Oncol. 99, 392–397. Thiery, J. P., Acloque, H., Huang, R. Y. J., and Nieto, M. A. (2009). Epithelial-Mesenchymal Transitions in Development and Disease. Cell 139, 871–890. Tian, K., Chen, P., Liu, Z., Si, S., Zhang, Q., Mou, Y., Han, L., Wang, Q., and Zhou, X. (2017). Sirtuin 6 inhibits epithelial to mesenchymal transition during idiopathic pulmonary fibrosis via inactivating TGF-β1/Smad3 signaling. Oncotarget 8, 61011–61024. Tse, J. C., and Kalluri, R. (2007). Mechanisms of metastasis: Epithelial-to-mesenchymal transition and contribution of tumor microenvironment. J. Cell. Biochem. 101, 816–829. Wang, J., Wei, Q., Wang, X., Tang, S., Liu, H., Zhang, F., Mohammed, M. K., Huang, J., Guo, D., Lu, M., et al. (2016). Transition to resistance: An unexpected role of the EMT in cancer chemoresistance. Genes Dis. 3, 3–6. Witz, I. P. (2008). The selectin-selectin ligand axis in tumor progression. Cancer Metastasis Rev. 27, 19–30. Wong, M., Xu, G., Park, D., Barboza, M., and Lebrilla, C. B. (2018). Intact glycosphingolipidomic analysis of the cell membrane during differentiation yields extensive glycan and lipid changes. Sci. Rep. 8, 10993. Zhang, J., Liu, D., Feng, Z., Mao, J., Zhang, C., Lu, Y., Li, J., Zhang, Q., Li, Q., and Li, L. (2016). MicroRNA-138 modulates metastasis and EMT in breast cancer cells by targeting vimentin. Biomed. Pharmacother. 77, 135–141. Zhang, X., Li, Y., Zhang, Y., Song, J., Wang, Q., Zheng, L., and Liu, D. (2013). Beta-Elemene Blocks Epithelial-Mesenchymal Transition in Human Breast Cancer Cell Line MCF-7 through Smad3-Mediated Down-Regulation of Nuclear Transcription Factors. PLoS One 8. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/86277 | - |
dc.description.abstract | 乳癌是嚴重的全球性疾病之一,在臺灣每年約有10,000名女性被診斷出癌症,此外每年更是有約2,000名臺灣婦女死於乳癌。根據統計,乳癌轉移到次級器官是乳癌病患存活率下降的主要原因,然而乳癌轉移 (metastasis) 機制仍充滿未知。目前研究指出Globo-系列醣神經鞘脂質 (globo series glycosphingolipids) 中的SSEA3、SSEA4及Globo H專一表現於乳癌細胞表面。且前人文獻中發現若將乳癌細胞株MBA-MB-231 (ER-, PR- and HER2-) knockdown 合成SSEA3的酵素β-1, 3-半乳糖基轉移酶5 (B3GALT5) ,則會導致細胞降低遷移 (migration)及貼附 (adhesion) 的能力。因此本研究希望進一步釐清globo series glycosphingolipids在乳癌轉移過程中所扮演的角色。本試驗藉由乳癌細胞株MCF-7 (ER+¬, PR+ 以及GR+) 中過度表現B3GALT5,發現 MCF-7不僅展現上皮細胞的特色,並降低間葉細胞生物標的,同時也降低其細胞遷移與貼附的能力。此結果指示globo series glycosphingolipids在MCF-7及 MBA-MB-231中可能具有不同的功能。此外,我們發現過度表現B3GALT5所導致的細胞轉移能力缺失,可藉由knockdown合成Globo H的酵素FUT1達成修復,然而knockdown合成SSEA4的酵素ST3GAL2,卻無法修復此等功能。上述結果指示Globo H的表現可能會抑制MCF-7細胞轉移能力。總結來說,在MCF-7中過度表現B3GALT5會提升Globo H及SSEA4表現量而非SSEA3,但僅有Globo H表現量提升會抑制細胞遷移及貼附的能力。本試驗結果指出在不同乳癌細胞型態中,Globo-系列醣神經鞘脂質可能具有不同的功能,更進一步了解globo series glycosphingolipids在乳癌細胞轉移機制中所扮演的角色,將有助於乳癌治療策略的研發。 | zh_TW |
dc.description.abstract | Breast cancer is among the leading causes of death worldwide. In Taiwan, about 10,000 cases are diagnosed and approximately 2,000 women die from breast cancer per year. Despite the fact that metastasis is the major cause of cancer deaths, the underlying mechanisms remain poorly understood. SSEA3, SSEA4 and Globo H are globo series glycosphingolipids (GSLs) specifically expressed on the surface of breast cancer cells. Knockdown of β1,3-Galactosyltransferase 5 (B3GALT5), the enzyme catalyzes the formation of SSEA3, in breast cancer cell line MBA-MB-231 (negative for ER, PR and HER2), has been shown to decreases cell migration and adhesion. Hence, in this study, we aim to understand the roles of globo series GSLs and signaling pathways involved in breast cancer metastasis. By overexpression of B3GALT5 in breast cancer cell line MCF-7 (positive for ER, PR and GR), we found that MCF-7 not only exhibits features of epithelial cells, but also decreased cell migration, adhesion and the expression of mesenchymal markers. These results indicate that globo series GSLs might have different functions between MCF-7 and MBA-MB-231. In addition, overexpression of B3GALT5 in MCF-7 impaired cell migration and adhesion, which could be recovered by knockdown of FUT1, the Globo H biosynthetic enzyme. In contrast, knockdown of ST3GAL2, the SSEA4 biosynthetic enzyme, would not affect cell migration and adhesion in B3GALT5-overexpression cells. These data suggesting the expression of Globo H might inhibit the cell motility of MCF-7. Collectively, our findings indicated that overexpression of B3GALT5 in MCF-7 promotes the expression of Globo H and SSEA4 instead of SSEA3. Moreover, only the increasing of Globo H inhibits migration and adhesion of MCF-7 cells. The globo series GSLs might play different roles in different breast cancer cell types. Further understanding the mechanism of metastasis will help us to develop new therapeutic strategy for breast cancer. | en |
dc.description.provenance | Made available in DSpace on 2023-03-19T23:46:26Z (GMT). No. of bitstreams: 1 U0001-2208202210324200.pdf: 4081379 bytes, checksum: 2607a74192392ea78e6207fadc2782c3 (MD5) Previous issue date: 2022 | en |
dc.description.tableofcontents | 目次 致謝 i 摘要 ii Abstract iii 目次 v 圖次 vii 表次 ix 縮寫表 x 第一章 前言及文獻探討 1 1-1. 前言 2 1-2. 文獻探討 3 1-2-1. 乳癌 3 1-2-2. Epithelial mesenchymal transition (EMT) 及mesenchymal epithelial transition (MET) 4 1-2-3. 乳癌轉移 5 1-2-4. Globo series 醣神經鞘脂質 (glycosphingolipids, GSLs) 7 第二章 誘導乳癌細胞進行EMT對globo series GSLs及B3GLAT5之影響 13 2-1. 背景 14 2-2. 材料與方法 15 2-3. 結果 17 2-4. 討論 25 第三章 B3GLAT5對乳癌細胞轉移能力之影響 27 3-1. 背景 28 3-2. 材料與方法 29 3-3. 結果 33 3-4. 討論 48 第四章 乳癌細胞中globo series GSLs功能的探討 50 4-1. 前言 51 4-2. 材料與方法 52 4-3. 結果 55 4-4. 討論 70 綜合討論 72 總結與未來展望 74 參考文獻 75 附錄 83 | |
dc.language.iso | zh-TW | |
dc.title | "β-1, 3-半乳糖基轉移酶5及Globo-系列醣神經鞘脂質在MCF-7乳癌細胞遷移與貼附角色之探討" | zh_TW |
dc.title | The roles of β-1, 3-galactosyltransferasee 5 and globo series glycosphingolipids in MCF-7 breast cancer cells migration and adhesion | en |
dc.type | Thesis | |
dc.date.schoolyear | 110-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳全木(Chuan-Mu Chen),楊尚訓(Shang-Hsun Yang),游舒涵(Shu-Han Yu) | |
dc.subject.keyword | 乳癌,β-1, 3-半乳糖基轉移酶5,Globo-系列醣神經鞘脂質,細胞遷移,細胞貼附,MCF-7乳癌細胞株, | zh_TW |
dc.subject.keyword | breast cancer,B3GALT5,globo series glycosphingolipids,migration,adhesion,MCF-7 breast cancer cell line, | en |
dc.relation.page | 88 | |
dc.identifier.doi | 10.6342/NTU202202629 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2022-08-29 | |
dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
dc.contributor.author-dept | 生物科技研究所 | zh_TW |
dc.date.embargo-lift | 2022-09-05 | - |
顯示於系所單位: | 生物科技研究所 |
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