https://scholars.lib.ntu.edu.tw/handle/123456789/467170
標題: | C1GALT1 promotes invasive phenotypes of hepatocellular carcinoma cells by modulating integrin β1 glycosylation and activity | 作者: | Liu C.-H. REY-HENG HU Huang M.-J. I-RUE LAI Chen C.-H. HONG-SHIEE LAI YAO-MING WU MIN-CHUAN HUANG |
公開日期: | 2014 | 出版社: | Public Library of Science | 卷: | 9 | 期: | 8 | 起(迄)頁: | e94995 | 來源出版物: | PLoS ONE | 摘要: | Cancer cell invasion and metastasis are the primary causes of treatment failure and death in hepatocellular carcinoma (HCC). We previously reported that core 1 β1,3-galactosyltransferase (C1GALT1) is frequently overexpressed in HCC tumors and its expression is associated with advanced tumor stage, metastasis, and poor survival. However, the underlying mechanisms of C1GALT1 in HCC malignancy remain unclear. In this study, we found that overexpression of C1GALT1 enhanced HCC cell adhesion to extracellular matrix (ECM) proteins, migration, and invasion, whereas RNAi-mediated knockdown of C1GALT1 suppressed these phenotypes. The promoting effect of C1GALT1 on the metastasis of HCC cells was demonstrated in a mouse xenograft model. Mechanistic investigations showed that the C1GALT1-enhanced phenotypic changes in HCC cells were significantly suppressed by anti-integrin β1 blocking antibody. Moreover, C1GALT1 was able to modify O-glycans on integrin β1 and regulate integrin β1 activity as well as its downstream signaling. These results suggest that C1GALT1 could enhance HCC invasiveness through integrin β1 and provide novel insights into the roles of O-glycosylation in HCC metastasis. ? 2014 Liu et al. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84905493050&doi=10.1371%2fjournal.pone.0094995&partnerID=40&md5=d349765be50177d742ccd440714b7b72 https://scholars.lib.ntu.edu.tw/handle/123456789/467170 |
ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0094995 | SDG/關鍵字: | beta 1,3 galactosyltransferase; beta1 integrin; galactosyltransferase; integrin beta1 blocking antibody; protein antibody; scleroprotein; unclassified drug; beta1 integrin; C1GALT1 protein, human; galactosyltransferase; neutralizing antibody; polysaccharide; protein binding; scleroprotein; small interfering RNA; animal experiment; animal model; animal tissue; article; cell adhesion; cell invasion; cell migration; controlled study; enzyme activity; enzyme regulation; enzyme repression; female; gene overexpression; gene silencing; human; human cell; liver cell carcinoma; mouse; nonhuman; phenotype; protein analysis; protein function; protein glycosylation; RNA interference; tumor invasion; animal; antagonists and inhibitors; Carcinoma, Hepatocellular; cell motion; chemistry; drug effects; gene expression regulation; genetics; glycosylation; Liver Neoplasms, Experimental; Lung Neoplasms; metabolism; pathology; SCID mouse; secondary; signal transduction; tumor cell line; tumor invasion; Animals; Antibodies, Neutralizing; Antigens, CD29; Carcinoma, Hepatocellular; Cell Adhesion; Cell Line, Tumor; Cell Movement; Extracellular Matrix Proteins; Female; Galactosyltransferases; Gene Expression Regulation, Neoplastic; Glycosylation; Humans; Liver Neoplasms, Experimental; Lung Neoplasms; Mice; Mice, SCID; Neoplasm Invasiveness; Polysaccharides; Protein Binding; RNA, Small Interfering; Signal Transduction |
顯示於: | 解剖學暨細胞生物學科所 |
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