Core 1 β1,3 galactosyltransferase (C1GALT1 )影響乳癌細胞惡性行為之研究

The role of Core 1 β1,3 galactosyltransferase (C1GALT1) in breast cancer cell malignant behaviors

周志行(Chih-Hsing Chou)

指導教授 ： 黃敏銓

國立臺灣大學/醫學院/解剖學暨細胞生物學研究所/博士(2015年)

https://doi.org/10.6342/NTU.2015.02626

摘要

根據世界衛生組織公佈乳癌佔全球女性癌症發生率與死亡率皆排名第一位。異常的醣化修飾常見於許多癌症發展過程中。Core 1 β1,3-galactosyltransferase (C1GALT1)為為黏液型醣化作用過程中唯一可以形成Core 1 structure (Gal-GalNAc-Ser/The)的醣化酵素，並且在許多腫瘤形成的過程中被發現C1GALT1有大量表現。從許多公開的RNA Microarray資料庫中我們發現C1GALT1 mRNA在乳癌腫瘤中表現增加，並且顯示高表現C1GALT1的病人其10年存活率相較低表現的病人差。此外，我們利用乳癌Tissue Microarray觀察C1GALT1蛋白質表現量也顯示C1GALT1在乳癌腫瘤組織中有大量表現，並且其表現量與病人的病理因子Grade與Stage成正相關。從in vitro與in vivo實驗證實C1GALT1可以促進乳癌細胞的惡性行為之特性，例如：細胞遷移、侵襲、癌幹細胞特性以及生長；同樣地抑制C1GALT1表現則會降低其惡性行為。此外，C1GALT1可以調控MUC1-N上的醣化結構，並且透過影響其下游MUC1-C/β-catenin/ERK訊號路徑，來調控乳癌細胞生長。本篇研究指出C1GALT1在乳癌腫瘤形成過程中扮演重要角色，未來在真對乳癌治療研究上提供一個具潛力的方向。

關鍵字

乳癌 ； 黏液型醣化蛋白酶

並列摘要

Core 1 β1,3-galactosyltransferase (C1GALT1) is an exclusive enzyme in humans that catalyzes the biosynthesis of core 1 O-glycan structure, Gal-GalNAc-O-Ser/Thr, whose expression is commonly up-regulated during tumorigenesis. Aberrant glycosylation is frequently observed in cancers. Breast cancer is the most frequently diagnosed malignancy in women and the first leading cause of cancer-related death worldwide. However, little is known about the function of C1GALT1 in breast cancer. Breast cancer is the most frequently diagnosed malignancy in women and the first leading cause of cancer-related death worldwide. This study aims to establish the correlation between C1GALT1 expression and breast cancer clinicopathological features and the roles of C1GALT1 in breast cancer malignant phenotypes. Public databases and our data show that C1GALT1 mRNA and protein are frequently up-regulated in breast cancer; and increased C1GALT1 expression correlates with higher histological grade and advanced tumor stage. Overexpression of C1GALT1 enhanced breast cancer cell growth, migration, and invasion in vitro and tumor growth in vivo. Conversely, C1GALT1 knockdown suppressed these malignant phenotypes. Furthermore, C1GALT1 modulated O-glycan structures on Mucin (MUC) 1 and promoted MUC1-C/β-catenin signaling in breast cancer cells. These findings suggest that C1GALT1 enhances breast cancer malignant progression by promoting MUC1-C/β-catenin signaling pathway.

並列關鍵字

Breast cancer ； C1GALT1 ； MUC1

參考文獻

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