N-acetylglucosaminyltransferase V modulates radiosensitivity and migration of small cell lung cancer through epithelial-mesenchymal transition.
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 ZEB2 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 ZEB2 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 ZEB2). 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.
['Huang|Chunyue|C|', 'Huang|Miaojuan|M|', 'Chen|Wenxia|W|', 'Zhu|Weiliang|W|', 'Meng|Hui|H|', 'Guo|Linlang|L|', 'Wei|Ting|T|', 'Zhang|Jian|J|']
D000328:Adult D000368:Aged D000818:Animals D045744:Cell Line, Tumor D002465:Cell Movement D058750:Epithelial-Mesenchymal Transition D005260:Female D006801:Humans D008175:Lung Neoplasms D008297:Male D051379:Mice D008875:Middle Aged D017351:N-Acetylglucosaminyltransferases D019253:Proto-Oncogene Proteins c-bcl-2 D011836:Radiation Tolerance D055752:Small Cell Lung Carcinoma D051028:bcl-2-Associated X Protein
N-acetylglucosaminyltransferase V radiosensitivity migration small cell lung cancer epithelial-mesenchymal transition