B4GALT3在大腸癌細胞中的功能性角色

β4半乳糖轉移酵素(B4GALTs)能夠將雙磷酸尿苷-半乳糖(UDP-galactose)經由β-1,4-糖苷鍵結接到氨基乙醯葡萄糖苷(N-acetylglucosamine)之上而生成氨基乙醯乳糖苷(N-acetyllactosamine)。重複的氨基乙醯乳糖苷單元可組成的聚氨基乙醯乳糖苷(poly-N-acetyllactosamine)。在本研究中，我們闡明了β4半乳糖轉移酵素三號 (B4GALT3)在HCT116大腸癌細胞之功能性角色。過度表達B4GALT3促進了細胞在體外的增殖以及老鼠體內腫瘤的生長；同時，將細胞培養在懸浮環境時，過度表達B4GALT3也促進了細胞群落的形成。另外，過度表達 B4GALT3也降低了細胞遷移和侵襲能力。有趣的是，B4GALT3會增加表皮生長因子受體(EGFR)以及β1整合素(β1 integrin)上的poly-N-acetyllactosamine結構。在過度表達 B4GALT3的細胞中，我們發現了EGFR的845酪胺酸位置有較多的磷酸化現象(pY845)，這可能是促使細胞生長增加的原因。此外，B4GALT3會降低FAK和paxillin的磷酸化，這表示了導致細胞遷移能力下降的部分原因可能是藉由integrin信號傳導通路。經由免疫組織化學染色我們發現了在64.6% (7/11)大腸直腸癌病人中，B4GALT3是表現量上升的；然而，經由西方點墨法及定量聚合酵素鏈鎖反應，卻發現分別只有40% (4/10)和44.6% (37/83)的病人有B4GALT3表現量上升的現象。這種不一致性可能是由於一些在大腸黏膜的基質細胞也表現有B4GALT3所造成。

關鍵字

β4半乳糖轉移酵素；大腸直腸癌；表皮生長因子受體； β1 整合素

並列摘要

β-1,4-galactosyltransferases (B4GALTs) catalyze the transfer of UDP-galactose to an N-acetylglucosamine via β-1,4-linkage and are responsible for the biosynthesis of N-acetyllactosamine. Poly-N-acetyllactosamines are composed of repeating units of N-acetyllactosamine. In the present study, we elucidate the function of B4GALT3 in HCT116 colon cancer cells. Overexpression of B4GALT3 promotes cell proliferation in vitro and tumor growth in vivo, as well as colony formation. Overexpression of B4GALT3 also reduces cell migration and invasion. Interestingly, B4GALT3 increases poly-N-acetyllactosamine structures on both EGFR and β1 integrin. Up-regulation of phosphorylated EGFR (pY845) is found in cells overexpressing B4GALT3 and this may lead to an increase in cell growth. Moreover, B4GALT3 decreases phosphorylation of focal adhesion kinase (FAK) and paxillin, indicating that reduced cell migration may be partly mediated by integrin signaling pathways. Immunohistochemistry shows that B4GALT3 is up-regulated in 64.6% (7/11) of colorectal tumors compared with their normal counterparts, whereas only 40% (4/10) and 44.6% (37/83) detected by Western blotting and QPCR, respectively. This inconsistency may result from the positive staining of some stromal cells in colorectal mucosae.

並列關鍵字

β1,4-galactosyltransferase ； colorectal cancer ； EFGR ； β1 integrin

參考文獻

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B4GALT3在大腸癌細胞中的功能性角色

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