凝集素檢視肺癌病人血清顯示鈣黏蛋白醣化差異

Lectin Screening of Lung Cancer Patient Sera Reveal Changes of Glycosylation of E-cadherin Molecules

陳治達(Chih-Ta Chen)

指導教授 ： 周綠蘋

國立臺灣大學/醫學院/生物化學暨分子生物學研究所/碩士(2009年)

https://doi.org/10.6342/NTU.2009.00695

摘要

在真核細胞生物中，超過一半的蛋白質是被醣(glycosylation)的。不同的醣類修飾賦與蛋白各式各樣的功能，因此不同的醣蛋白參與著不同的細胞功能。而不同的醣化也對蛋白質產生不同的影響。它們可能影響蛋白質的穩定性(stability)；也可使得受修飾的蛋白質擁有辨認特定受質(ligands)的能力；甚至可以影響蛋白質的最終去處。換句話說，醣蛋白上的醣修飾產生異常變化將對蛋白本身的功能產生重大的影響。
鈣黏蛋白(E-cadherin)是組成細胞間黏著接合(adherent junction)主要成分之ㄧ。他也是在與β 索烴素(β-catenin)和α 索烴素(α-catenin)行成的複合體(complex) 中主要的成分。根據報導， 鈣黏蛋白是個腫瘤抑制物(tumor suppressor)。而適當的維持鈣黏蛋白的正常功能對於細胞移動力(motility)的調節是很重要的一環。
在本研究中，我們利用凝集素染色法(lectin staining)檢視鈣黏蛋白的醣化變化。結果指出， 鈣黏蛋白上的醣內容物確實改變了。其中，藻岩醣化(fucosylation)的改變是最顯著的。在肺癌病人中，鈣黏蛋白的藻岩醣化有增高趨勢，且隨著期別演進而上升。在細胞層次上，鈣黏蛋白也被觀察到有藻岩醣化的現象。與先前的研究資料比對分析後，我們認為鈣黏蛋白的藻岩醣化與其截斷(truncation) 可能有某種程度上的關係。再進一步的分析藻岩醣轉移酶(fucosyltransferase)的表現量，我們發現鈣粘蛋白的藻岩醣化可能與其中一個轉移酶FUT8 過度表現有關。

關鍵字

鈣粘蛋白 ； 藻岩醣化 ； 醣蛋白 ； 截斷 ； 移動力

並列摘要

In eukaryotes, more than half of the proteins are gylcosylated. Different types of sugar modification would grant the protein diverse functions. Hence, different
glycoproteins involve in different fields of cellular functions. Various glycosylations exert different effect on the proteins. They may affect the stability of the protein; they could grant their protein hosts the ability to recognize specific ligands; even, they can decide the destination of the protein. In other words, aberration of the carbohydrate content of these glycoproteins would result to great impact on their functions.
E-cadherin is the main component of adherent junction among cells. It is also the major member of the complex formed with -catenin, -catenin, and others. It has been
reported that E-cadherin is a tumor suppressor. Proper retaining of its normal function is crucial to regulation of cell motility.
In our study, we screened glycosylation change of E-cadherin by lectin staining. As data indicated, the sugar content of E-cadherin had changed. Fucosylation alteration
is the most notable one. E-cadherin fucosylation is elevated in lung cancer, and the trend goes up with stages. In cell lines, E-cadherin fucosylation was also seen. Compared with previous data, we speculated that E-cadherin fucosylation may be in relation to its truncation. Further examination of fucosyltransferase gene, we assumed that E-cadherin fucosylation of E-cadherin might result from overexpression of FUT8.

並列關鍵字

E-cadherin ； fucosylation ； glycoprotein ； truncation ； motility

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