title: Up-regulation of C1GALT1 promotes breast cancer cell growth through MUC1-C signaling pathway.
abstract: 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.
authors.affiliation: Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chih-Hsing
authors.initials: CH
authors.lastname: Chou
authors.affiliation: Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Miao-Juei
authors.initials: MJ
authors.lastname: Huang
authors.affiliation: Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chi-Hau
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ming-Kwang
authors.initials: MK
authors.lastname: Shyu
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: John
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ji-Shiang
authors.initials: JS
authors.lastname: Hung
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chiun-Sheng
authors.initials: CS
authors.lastname: Huang
authors.affiliation: Graduate Institute of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.|Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Min-Chuan
authors.initials: MC
authors.lastname: Huang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D005700:Galactosyltransferases / Q000235:genetics / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D015854:Up-Regulation; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C060192:MUC1 protein, human; D018396:Mucin-1; D051176:beta Catenin; C505293:C1GALT1 protein, human; D005700:Galactosyltransferases
keywords: C1GALT1; MUC1; T antigen; beta-catenin; breast cancer