title: HIF-1α induces the epithelial-mesenchymal transition in gastric cancer stem cells through the Snail pathway.
abstract: Substantial evidence suggests that the epithelial-mesenchymal transition (EMT) phenotype is associated with the invasive characteristics of cancer stem cells (CSCs),which possess an EMT phenotype that may predominate in tumor invasion and metastasis. However, the mechanisms for the generation and regulation of these CSCs have not been clearly defined. As hypoxia and EMT-related factors may have important functions in EMT-like CSCs, the aim of this study was to investigate the effects of hypoxia on these cells. CSCs were established from the gastric cancer cell lines MGC-803 and SGC7901, and the relationship between hypoxia and EMT-like CSCs was investigated in gastric cancer. After hypoxia treatment, some gastric CSCs exhibited a marked increase in hypoxia-inducible factor-1α (HIF-1α)expression and increased migration and invasion capabilities compared with the normoxic control. These CSCs were defined by activation of the mesenchymal cell marker Vimentin and by inhibition of the epithelial cell marker E-cadherin. Our analyses also show that HIF-1α was responsible for activating EMT via increased expression of the transcription factor Snail in gastric CSCs. Moreover, inhibition of Snail by shRNA reduced HIF-1α-induced EMT in gastric CSCs. The results demonstrated that hypoxia-induced EMT-like CSCs rely on HIF-1αto activate Snail, which may result in recurrence and metastasis of gastric cancer.
authors.affiliation: Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Shi-Wei
authors.initials: SW
authors.lastname: Yang
authors.affiliation: Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Zhang
authors.affiliation: Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Ying-Xue
authors.initials: YX
authors.lastname: Hao
authors.affiliation: Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yong-Liang
authors.initials: YL
authors.lastname: Zhao
authors.affiliation: Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
authors.affiliation: Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Ping-Ang
authors.initials: PA
authors.lastname: Li
authors.affiliation: Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Chun-Yang
authors.initials: CY
authors.lastname: Liu
authors.affiliation: Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Pei-Wu
authors.initials: PW
authors.lastname: Yu
mesh_terms: D000818:Animals; D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D047368:Tumor Burden; D000072258:Tumor Hypoxia; D059016:Tumor Microenvironment; D014746:Vimentin / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000071250:Snail Family Transcription Factors; D014746:Vimentin
keywords: Snail; cancer stem cells (CSCs); epithelial–mesenchymal transition (EMT); hypoxia inducible factor-1α (HIF-1α)