Up-regulation of C1GALT1 promotes breast cancer cell growth through MUC1-C signaling pathway
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Chih-Hsing Chou1, Miao-Juei Huang1, Chi-Hau Chen2, Ming-Kwang Shyu2, John Huang3, Ji-Shiang Hung3, Chiun-Sheng Huang3, Min-Chuan Huang1,4
1Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan
2Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan
3Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
4Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan
Chiun-Sheng Huang, e-mail: [email protected]
Min-Chuan Huang, e-mail: [email protected]
Keywords: Breast cancer, C1GALT1, T antigen, MUC1, beta-catenin
Received: September 10, 2014 Accepted: January 06, 2015 Published: January 27, 2015
Aberrant glycosylation is frequently observed in cancers. 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. Little is known about the function of C1GALT1 in breast cancer. This study aims to determine the correlation between C1GALT1 expression and breast cancer clinicopathological features and roles of C1GALT1 in breast cancer malignant phenotypes. Public databases and our data showed that C1GALT1 mRNA and C1GALT1 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 as well as tumor growth in vivo. Conversely, C1GALT1 knockdown suppressed these malignant phenotypes. Furthermore, C1GALT1 modulates O-glycan structures on Mucin (MUC) 1 and promotes MUC1-C/β-catenin signaling in breast cancer cells. These findings suggest that C1GALT1 enhances breast cancer malignant progression through promoting MUC1-C/β-catenin signaling pathway. Unveiling the function of C1GALT1 in breast cancer opens new insights to the roles of C1GALT1 and O-glycosylation in tumorigenesis and renders the potential of C1GALT1 as a target of novel therapeutic agent development.
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