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N ‐acetylglucosaminyltransferase V modulates radiosensitivity and migration of small cell lung cancer through epithelial–mesenchymal transition
Author(s) -
Huang Chunyue,
Huang Miaojuan,
Chen Wenxia,
Zhu Weiliang,
Meng Hui,
Guo Linlang,
Wei Ting,
Zhang Jian
Publication year - 2015
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13419
Subject(s) - radiosensitivity , vimentin , epithelial–mesenchymal transition , gene knockdown , apoptosis , cancer research , cell migration , biology , cell , downregulation and upregulation , medicine , immunology , radiation therapy , gene , immunohistochemistry , biochemistry
N ‐acetylglucosaminyltransferase V (Gnt‐V) has been linked to the migration of various human cancers. Recently we have found that inhibition of Gnt‐V increases the radiosensitivity of cancer cells. However, the mechanisms by which Gnt‐V mediates radiosensitivity and migration, especially in small cell lung cancer ( SCLC ) remain unknown. In our study, two SCLC cell lines (H1688 and H146) were used to investigate whether Gnt‐V modulated the radiosensitivity and migration of SCLC cells through the epithelial–mesenchymal transition ( EMT ). The results showed that the expression of Gnt‐V correlated with the N stage in patients with SCLC . Overexpression of Gnt‐V led to a further increase in the relative viable cell number and survival fraction with a decrease in apoptosis rate and Bax/Bcl‐2 ratio, when the cells were treated with irradiation. By contrast, knockdown of Gnt‐V with irradiation resulted in a further decrease in the relative viable cell number and survival fraction but an increase in apoptosis rate and Bax/Bcl‐2 ratio. Cells expressing high levels of Gnt‐V increased migration whereas low levels of Gnt‐V suppressed cell migration. Besides, the transient knockdown of ZEB 2 led to an increase in radiosensitivity and an inhibition in the migration of SCLC cells. Furthermore, Gnt‐V was negatively correlated with E‐cadherin expression but positively correlated with N‐cadherin, vimentin and ZEB 2 expression. Finally, an in vivo study revealed that upregulation of Gnt‐V caused tumour growth more quickly, as well as the expression of EMT ‐related markers (N‐cadherin, vimentin and ZEB 2). Taken together, the study suggested that an elevation of Gnt‐V could lead to the radiosensitivity and migration of SCLC cells by inducing EMT , thereby highlighting Gnt‐V as a potential therapeutic target for the prevention of EMT ‐associated tumour radioresistance and migration.