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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 鄭永銘(Yung-Ming Jeng) | |
| dc.contributor.author | Ting-Huan Wang | en |
| dc.contributor.author | 王庭歡 | zh_TW |
| dc.date.accessioned | 2021-06-16T10:34:41Z | - |
| dc.date.available | 2015-09-24 | |
| dc.date.copyright | 2013-09-24 | |
| dc.date.issued | 2013 | |
| dc.date.submitted | 2013-08-14 | |
| dc.identifier.citation | 1. El-Serag HB, Rudolph KL (2007) Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132: 2557-2576.
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(2004) FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat Cell Biol 6: 154-161. 50. Logan CY, Nusse R (2004) The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 20: 781-810. 51. Schlessinger K, Hall A, Tolwinski N (2009) Wnt signaling pathways meet Rho GTPases. Genes Dev 23: 265-277. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/60884 | - |
| dc.description.abstract | CTHRC1為一種分泌型醣蛋白，且能活化Wnt 訊息傳遞的細胞極化路徑。使用微陣列分析，我們發現CTHRC1基因在肝癌中會過度表現。從201位肝癌病人取得手術切除的肝臟檢體，以即時反轉錄聚合反應分析mRNA表現量，我們發現在腫瘤體積較大以及癌症晚期者，CTHRC1表現量最為顯著。此外，CTHRC1表現量是一個肝癌不良預後的因子。
我們發現在肝癌細胞中過度表現CTHRC1能促進腫瘤侵犯能力。反之，將CTHRC1表現量降低，會抑制腫瘤移行與侵犯能力。更進一步探討，我們發現CTHRC1會誘發RhoA蛋白的活化而非Rac1或Cdc42，以促進細胞移行。CTHRC1藉由活化β1-integrin / FAK / ERK訊息傳遞路徑，增加細胞貼附能力以提升腫瘤轉移及侵犯能力。CTHRC1扮演著調節者的角色，藉由增進腫瘤細胞的貼附力與移行力來強化其侵犯與轉移的機會。我們也發現CTHRC1是一個新的評估肝癌病人預後因子。 | zh_TW |
| dc.description.abstract | Collagen triple helix repeat containing-1 (CTHRC1) is a secreted glycoprotein that activates the planar cell polarity pathway of Wnt signaling. Using microarray analysis, we found that the CTHRC1 gene is overexpressed in hepatocellular carcinoma (HCC). The level of CTHRC1 mRNA was measured in 201 surgically resected HCCs using real time reverse transcription-polymerase chain reaction. Overexpression of CTHRC1 in HCC was associated with large tumor size and advanced tumor stage. CTHRC1 overexpression predicts poor prognosis for HCC patients. Suppression of CTHRC1 expression inhibited tumor migration and invasion whereas overexpression of CTHRC1 promoted tumor invasion. Activation of RhoA, but not Rac1 or Cdc42, was found to play a crucial role in CTHRC1-induced cell migration. CTHRC1 promoted adhesion of cancer cells to extracellular matrix through induction of integrin β1 expression and activation of focal adhesion kinase. These results suggest CTHRC1 promotes tumor invasion and metastasis by enhancing the adhesion and migratory abilities of tumor cells. It is also a promising biomarker for predicting the prognosis of patients with HCC. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T10:34:41Z (GMT). No. of bitstreams: 1 ntu-102-R00444004-1.pdf: 3705914 bytes, checksum: a5df87f5387dddf2abca256737d1e280 (MD5) Previous issue date: 2013 | en |
| dc.description.tableofcontents | 口試委員會審定書 #
誌謝 I 中文摘要 II ABSTRACT III CONTENTS IV LIST OF FIGURES VI LIST OF TABLES VII Chapter 1 INTRODUCTION 1 1.1 Hepatocellular carcinoma 1 1.2 Collagen triple helix repeat containing 1 1 1.2.1 CTHRC1 is involved in Wnt pathway 2 1.2.2 CTHRC1 and disease 2 1.3 CTHRC1 in cancer 3 1.4 Regulation of cell migration 3 1.4.1 Integrin Family 4 1.4.2 FAK and focal adhesion 5 1.5 Purpose of Study 5 Chapter 2 MATERIAL AND METHODS 7 2.1 Liver samples 7 2.2 Histology study and tumor staging 7 2.3 Microarray analysis 8 2.4 RNA isolation and real time RT-PCR 8 2.5 Cell culture and treatment 9 2.6 Plasmid, transfection, and retroviral infection 9 2.7 Tumorigenicity assay 9 2.8 Boyden chamber assay 10 2.9 Adhesion assay 10 2.10 Immunofluorescence staining 11 2.11 Western blot 11 2.12 Detection of CTHRC1 in culture medium 12 2.13 3D collagen gel invasion assay 12 2.14 Flow cytometry 12 2.15 TOP/FOP Luciferase Reporter Assay 13 Chapter 3 RESULTS 14 3.1 CTHRC1 was overexpressed in HCC 14 3.2 CTHRC1 has no effect on cell proliferation 15 3.3 CTHRC1 overexpression increased tumor cell migration and invasion ability 15 3.4 CTHRC1 enhanced cell adhesion 16 3.5 CTHRC1 enhanced cell adhesion by enahncing β1-integrin expression 17 3.6 CTHRC1 has no effect on canonical Wnt pathway in HCC 18 Chapter 4 DISCUSSION 19 Chapter 5 FIGURES AND TABLES 23 5.1 Figures 23 5.2 Tables 42 REFERENCE 43 | |
| dc.language.iso | en | |
| dc.title | CTHRC1在肝癌中過度表現並促進癌症侵犯及轉移 | zh_TW |
| dc.title | CTHRC1 overexpression in hepatocellular carcinoma
promotes tumor invasion and metastasis | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 101-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 毛翠蓮(Tsui-Lien Mao),陳彥榮(Yen-Rong Chen),許晉銓(Jinn-Chyuan Sheu) | |
| dc.subject.keyword | 貼附,侵犯,轉移, | zh_TW |
| dc.subject.keyword | adhesion,invasion,FAK, | en |
| dc.relation.page | 45 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2013-08-14 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 病理學研究所 | zh_TW |
| 顯示於系所單位： | 病理學科所 | |
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