title: Sialylated β1, 6 branched N-glycans modulate the adhesion, invasion and metastasis of hepatocarcinoma cells.
abstract: The mouse hepatocarcinoma cell lines Hca-F and Hca-P have been derived from hepatocarcinoma in mice and metastasize only to the lymph node. Hca-F cells displayed greater lymphatic metastasis ability than Hca-P cells. When the two cell lines were compared for cell surface sialylated β1,6 branched N-glycans by flow cytometry using L-PHA and SNA, Hca-F cells were found to express significantly higher levels. To explore the effect of increased sialylated β1,6 branched N-glycans on hepatocarcinoma progression, we inhibit their expression in Hca-F cells by using swainsonine treatment and RNA interference. We found that swainsonine treatment or GnT-V-shRNA transfection significantly inhibited the formation of β1,6 branched N-glycans, and partially inhibited the expression of α2,6 sialic acids. Knockdown of sialylated β1,6 branched N-glycans significantly attenuated the invasive and metastatic capability both in vitro and in vivo. Blockade of α2,6 sialic acid expression on Hca-F cell surface by the treatment with neuraminidase caused reduction in cellular adherence to lymph node. In addition, knockdown of sialylated β1,6 branched N-glycans could decrease the expression of Notch1, NICD1, NICD2 and HES1 in Hca-F cells. Collectively, these findings suggest that increased sialylated β1,6 branched N-glycans may contribute to hepatocarcinoma progression by altering the adhesive, invasive and metastatic ability to lymph node via Notch signaling pathway.
authors.affiliation: Department of Pathology, Dalian Medical University, Dalian 116044, Liaoning Province, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian 116044, Liaoning Province, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian 116044, Liaoning Province, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Life Science and Medicine, Dalian University of Technology, Panjin 124221, Liaoning, China.
authors.forename: Xixi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian 116044, Liaoning Province, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian 116044, Liaoning Province, China.
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian 116044, Liaoning Province, China.
authors.forename: Qingmin
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Glycobiology, Dalian Medical University, Dalian 116044, Liaoning Province, China. Electronic address: wangshujing@dlmedu.edu.cn.
authors.forename: Shujing
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology*; D051379:Mice; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011134:Polysaccharides / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D017026:Swainsonine / Q000494:pharmacology; D014162:Transfection
chemical_list: D011134:Polysaccharides; D034741:RNA, Small Interfering; D051880:Receptors, Notch; D017351:N-Acetylglucosaminyltransferases; C510765:N-acetylglucosaminyltransferase IX, mouse; D019158:N-Acetylneuraminic Acid; D017026:Swainsonine
keywords: Hepatocarcinoma; Notch signaling; Sialic acids; β1,6 Branched N-glycans