title: N-acetylglucosaminyltransferase V modulates radiosensitivity and migration of small cell lung cancer through epithelial-mesenchymal transition.
abstract: 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.
authors: Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors: Chunyue
authors: C
authors: Huang
authors: Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors: Miaojuan
authors: M
authors: Huang
authors: Department of Radiotherapy, Longgang District Central Hospital of Shenzhen, China.
authors: Wenxia
authors: W
authors: Chen
authors: Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors: Weiliang
authors: W
authors: Zhu
authors: Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors: Hui
authors: H
authors: Meng
authors: Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors: Linlang
authors: L
authors: Guo
authors: Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors: Ting
authors: T
authors: Wei
authors: Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors: Jian
authors: J
authors: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D008875:Middle Aged; D017351:N-Acetylglucosaminyltransferases / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011836:Radiation Tolerance; D055752:Small Cell Lung Carcinoma / Q000201:enzymology* / Q000473:pathology / Q000532:radiotherapy*; D051028:bcl-2-Associated X Protein / Q000032:analysis
chemical_list: C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase
keywords: N-acetylglucosaminyltransferase V; epithelial-mesenchymal transition; migration; radiosensitivity; small cell lung cancer