Altered beta 1,6-GlcNAc branched N-glycans impair TGF-beta-mediated Epithelial-to-Mesenchymal Transition through Smad signalling pathway in human lung cancer

	Altered beta 1,6-GlcNAc branched N-glycans impair TGF-beta-mediated Epithelial-to-Mesenchymal Transition through Smad signalling pathway in human lung cancer
	Li, N; Xu, HN; Fan, K; Liu, XJ; Qi, JJ; Zhao, C; Yin, P; Wang, LY; Li, ZX; Zha, XL
刊名	JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
	2014
卷号	18 期号:10 页码:1975-1991
关键词	GnT-V N-glycans lung cancer EMT TGF-1
通讯作者	Li, ZX (reprint author), Fudan Univ, Dept Biochem & Mol Biol, Shanghai Med Coll, 138 Yi Xue Yuan Rd, Shanghai 200032, Peoples R China.,lizengxia@fudan.edu.cn ; xlzha@shmu.edu.cn
英文摘要	The change of oligosaccharide structure has been revealed to be crucial for glycoproteins' biological functions and cell biological characteristics. N-acetylglucosaminy transferase V (GnT-V), a key enzyme catalysing the reaction of adding 1, 6-N-acetylglucosamine (GlcNAc) on asparagine-linked oligosaccharides of cell proteins, has been implicated to a metastastic-promoting oncoprotein in some carcinomas. However, this correlation might not be subjected to all types of cancers, for example, in non-small cell lung cancers, low level of GnT-V expression is associated with relatively short survival time and poor prognosis. To explain the role of GnT-V in lung cancer progression, we studied the association of GnT-V expression with lung cancer EMT behaviour. We found that GnT-V expression was correlated with epithelial marker positively and mesenchymal marker negatively. GnT-V levels, as well as 1,6-GlcNAc branched N-glycans, were strongly reduced in TGF-1-induced EMT of human lung adenocarcinoma A549 cells. Further studies showed that suppression of 1,6-GlcNAc branched N-glycans by inhibitor or GnT-V silencing in A549 cells could promote TGF-1-induced EMT-like changes, cell migration and invasion. Meanwhile, overexpression of GnT-V impaired TGF-1-induced EMT, migration and invasion. It suggests that GnT-V suppresses the EMT process of lung cancer cells through inhibiting the TGF-/Smad signalling and its downstream transcription factors in a GnT-V catalytic activity-dependent manner. Taken together, the present study reveals a novel mechanism of GnT-V as a suppressor of both EMT and invasion in human lung cancer cells, which may be useful for fully understanding N-glycan's biological roles in lung cancer progression.
学科主题	Cell Biology; Research & Experimental Medicine
类目[WOS]	Cell Biology ; Medicine, Research & Experimental
关键词[WOS]	FOCAL ADHESION KINASE ; ACETYLGLUCOSAMINYLTRANSFERASE-V ; TUMOR PROGRESSION ; CELL-LINES ; LINKED OLIGOSACCHARIDES ; BREAST-CARCINOMA ; GENE-EXPRESSION ; MESSENGER-RNA ; GROWTH ; GLYCOSYLATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000343739200007
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/235]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Li, N,Xu, HN,Fan, K,et al. Altered beta 1,6-GlcNAc branched N-glycans impair TGF-beta-mediated Epithelial-to-Mesenchymal Transition through Smad signalling pathway in human lung cancer[J]. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,2014,18(10):1975-1991.
APA	Li, N.,Xu, HN.,Fan, K.,Liu, XJ.,Qi, JJ.,...&Zha, XL.(2014).Altered beta 1,6-GlcNAc branched N-glycans impair TGF-beta-mediated Epithelial-to-Mesenchymal Transition through Smad signalling pathway in human lung cancer.JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,18(10),1975-1991.
MLA	Li, N,et al."Altered beta 1,6-GlcNAc branched N-glycans impair TGF-beta-mediated Epithelial-to-Mesenchymal Transition through Smad signalling pathway in human lung cancer".JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 18.10(2014):1975-1991.