|Title:||Up-regulation of C1GALT1 promotes breast cancer cell growth through MUC1-C signaling pathway||Authors:||Chou C.-H.
|Issue Date:||2015||Publisher:||Impact Journals LLC||Journal Volume:||6||Journal Issue:||8||Start page/Pages:||6123-6135||Source:||Oncotarget||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.
|ISSN:||1949-2553||DOI:||10.18632/oncotarget.3045||SDG/Keyword:||beta catenin; core 1 beta1,3 galactosyltransferase; galactosyltransferase; glycoprotein; messenger RNA; mucin 1C; small interfering RNA; unclassified drug; beta catenin; C1GALT1 protein, human; galactosyltransferase; MUC1 protein, human; mucin 1; animal experiment; animal model; animal tissue; Article; breast cancer; breast cancer cell line; breast carcinoma; C1GALT1 gene; cancer grading; cancer growth; cancer inhibition; cancer staging; cell migration; controlled study; correlation analysis; female; gene silencing; human; human tissue; in vitro study; in vivo study; mouse; nonhuman; protein expression; protein function; protein glycosylation; signal transduction; tumor invasion; tumor promotion; upregulation; animal; breast tumor; enzymology; genetic transfection; genetics; metabolism; pathology; SCID mouse; signal transduction; tumor cell line; xenograft; Animals; beta Catenin; Breast Neoplasms; Cell Line, Tumor; Female; Galactosyltransferases; Heterografts; Humans; Mice; Mice, SCID; Mucin-1; Signal Transduction; Transfection; Up-Regulation
|Appears in Collections:||解剖學暨細胞生物學科所|
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