TY - JOUR
T1 - Altered β1,6-GlcNAc branched N-glycans impair TGF-β-mediated Epithelial-to-Mesenchymal Transition through Smad signalling pathway in human lung cancer
AU - Li, Na
AU - Xu, Haineng
AU - Fan, Kun
AU - Liu, Xijun
AU - Qi, Jingjing
AU - Zhao, Chao
AU - Yin, Peng
AU - Wang, Liying
AU - Li, Zengxia
AU - Zha, Xiliang
N1 - Publisher Copyright:
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - 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 β1, 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 β1,6-GlcNAc branched N-glycans, were strongly reduced in TGF-β1-induced EMT of human lung adenocarcinoma A549 cells. Further studies showed that suppression of β1,6-GlcNAc branched N-glycans by inhibitor or GnT-V silencing in A549 cells could promote TGF-β1-induced EMT-like changes, cell migration and invasion. Meanwhile, overexpression of GnT-V impaired TGF-β1-induced EMT, migration and invasion. It suggests that GnT-V suppresses the EMT process of lung cancer cells through inhibiting the TGF-β/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.
AB - 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 β1, 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 β1,6-GlcNAc branched N-glycans, were strongly reduced in TGF-β1-induced EMT of human lung adenocarcinoma A549 cells. Further studies showed that suppression of β1,6-GlcNAc branched N-glycans by inhibitor or GnT-V silencing in A549 cells could promote TGF-β1-induced EMT-like changes, cell migration and invasion. Meanwhile, overexpression of GnT-V impaired TGF-β1-induced EMT, migration and invasion. It suggests that GnT-V suppresses the EMT process of lung cancer cells through inhibiting the TGF-β/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.
KW - EMT
KW - GnT-V
KW - Lung cancer
KW - N-glycans
KW - TGF-β1
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U2 - 10.1111/jcmm.12331
DO - 10.1111/jcmm.12331
M3 - Article
C2 - 24913443
AN - SCOPUS:84908074963
SN - 1582-1838
VL - 18
SP - 1975
EP - 1991
JO - Journal of Cellular and Molecular Medicine
JF - Journal of Cellular and Molecular Medicine
IS - 10
ER -