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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/58311
標題: | "β-1,4-galactosyltransferase III抑制β1 integrin調控之大腸直腸癌細胞侵入行為且與大腸直腸癌轉移為負相關" β-1,4-Galactosyltransferase III suppresses β1 integrin mediated invasive phenotypes and negatively correlates with metastasis in colorectal cancer |
作者: | Chia-Hua Chen 陳家嬅 |
指導教授: | 黃敏銓(Min-Chuan Huang) |
關鍵字: | 醣化,轉移,細胞入侵, B4GALT3,β1 integrin,poly-N-acetyllactosamine,glycosylation,metastasis,invasion, |
出版年 : | 2014 |
學位: | 博士 |
摘要: | 大腸直腸癌(CRC)的病人中常常發生癌細胞轉移,且癌細胞轉移為治療癌症主要的困難所在。在CRC病人中,poly-N-acetyllactosamine相關醣類結構有大量表現上升的情況,且與癌症的形成和轉移有關。B4GALT3是一個調控poly-N-acetyllactosamine製造的酵素,因此我們研究其在CRC中的表現。我們發現B4GALT3的表現與病人的癌組織不良分化(P < 0.001)、癌症末期(P = 0.0052)、區域性淋巴結轉移(P = 0.0018)及遠端轉移(P = 0.0463)呈現負相關。過度表現B4GALT3在CRC細胞株中可以抑制細胞遷移、細胞入侵及附著,而減弱B4GALT3在細胞中的表現量則會增進細胞惡性之行為。加入可以抑制β1 integrin活化的抗體可以反轉B4GALT3所造成細胞入侵的增加。 B4GALT3的表現可以改變β1 integrin上N-glycan的醣化,可能是改變poly-N-acetyllactosamine的表現。此外,減弱B4GALT3在細胞中的表現量則會造成更多β1 integrin及其下游的訊息傳遞的活化,另一方面大量表現B4GALT3則會抑制活化的β1 integrin表現及其下的訊息傳遞。我們的結果說明B4GALT3與CRC的轉移呈現負相關,且經由抑制β1 integrin的活化來減低細胞的入侵能力。 Metastasis often occurs in colorectal cancer (CRC) patients and is the main difficulty in cancer treatment. The upregulation of poly-N-acetyllactosamine related glycosylation is found in CRC patients and is associated with progression and metastasis in cancer. B4GALT3 is an enzyme responsible for poly-N-acetyllactosamine synthesis, and therefore we investigated its expression in CRC patients. We found that B4GALT3 negatively correlated with poorly differentiated histology (P < 0.001), advanced stages (P = 0.0052), regional lymph node metastasis (P = 0.0018), and distant metastasis (P = 0.0463) in CRC patients. B4GALT3 overexpression in CRC cells suppressed cell migration, invasion, and adhesion, while B4GALT3 knockdown enhanced malignant cell phenotypes. The β1 integrin blocking antibody reversed the B4GALT3-mediated increase in cell invasion. B4GALT3 expression altered glycosylation on the N-glycan of β1 integrin probably through changes in poly-N-acetyllactosamine expression. Furthermore, more activated β1 integrin along with the activation of its downstream signaling transduction were found in B4GALT3-knockdown cells, whereas overexpression of B4GALT3 suppressed the expression of active β1 integrin and inhibited its downstream signaling. Our results suggest that B4GALT3 is negatively associated with CRC metastasis and suppresses cell invasiveness through inhibiting activation of β1 integrin. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/58311 |
全文授權: | 有償授權 |
顯示於系所單位: | 解剖學暨細胞生物學科所 |
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