title: Hypoxia induced epithelial-mesenchymal transition and vasculogenic mimicry formation by promoting Bcl-2/Twist1 cooperation.
abstract: Hypoxia plays a pivotal role in tumor progression. The functions of hypoxia and subsequent Bcl-2/Twist1 activation in epithelial-mesenchymal transition (EMT) and vasculogenic mimicry (VM) formation are currently unclear. This study aimed to investigate the role of Bcl-2/Twist1 cooperation in hypoxia-induced EMT and VM formation. In in vitro experiments, we found that hypoxia resulted in co-overexpression of Bcl-2 and Twist1, facilitated Twist1 nuclear translocation and promoted EMT and VM formation. Co-overexpression of Bcl-2 and Twist1 under normoxia could also induce EMT and promote VM formation. Furthermore, blocking Bcl-2 or Twist1 attenuated the effects of hypoxia on EMT progress and VM formation in hepatocellular carcinoma cells. In in vivo experiments, the mechanism by which hypoxia promoted Bcl-2 and Twist1 co-overexpression and induced EMT process and VM formation was demonstrated using murine xenograft models. These results above suggest that hypoxia could activate the cooperation of Bcl-2 and Twist1, Bcl-2 plays an important role in assisting Twist1 nuclear translocation which could change the expression of a wide range of genes and lead to the induction of EMT and VM formation.
authors: Department of Pathology, Tianjin Medical University, Tianjin 300070, China. Electronic address: liukun5461@126.com.
authors: Kun
authors: K
authors: Liu
authors: Department of Pathology, Tianjin Medical University, Tianjin 300070, China; Department of Pathology, Tianjin General Hospital, Tianjin Medical University, Tianjin 300052, China; Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin 300060, China. Electronic address: baocunsun@gmail.com.
authors: Baocun
authors: B
authors: Sun
authors: Department of Pathology, Tianjin Medical University, Tianjin 300070, China; Department of Pathology, Tianjin General Hospital, Tianjin Medical University, Tianjin 300052, China. Electronic address: xiulanzhao5892@126.com.
authors: Xiulan
authors: X
authors: Zhao
authors: Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin 300060, China. Electronic address: xudongwang01@126.com.
authors: Xudong
authors: X
authors: Wang
authors: Department of Pathology, Tianjin Medical University, Tianjin 300070, China; Department of Pathology, Tianjin General Hospital, Tianjin Medical University, Tianjin 300052, China. Electronic address: yanleili0@126.com.
authors: Yanlei
authors: Y
authors: Li
authors: Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin 300060, China. Electronic address: zqqiubb@163.com.
authors: Zhiqiang
authors: Z
authors: Qiu
authors: Department of Pathology, Tianjin Medical University, Tianjin 300070, China; Department of Pathology, Tianjin General Hospital, Tianjin Medical University, Tianjin 300052, China. Electronic address: qiang00gu@163.com.
authors: Qiang
authors: Q
authors: Gu
authors: Department of Pathology, Tianjin Medical University, Tianjin 300070, China; Department of Pathology, Tianjin General Hospital, Tianjin Medical University, Tianjin 300052, China. Electronic address: xueyidongdong@126.com.
authors: Xueyi
authors: X
authors: Dong
authors: Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University, Tianjin 300060, China. Electronic address: yanhuizhanglove@163.com.
authors: Yanhui
authors: Y
authors: Zhang
authors: Department of Pathology, Tianjin Medical University, Tianjin 300070, China. Electronic address: wangcongcong2011@sina.com.
authors: Yong
authors: Y
authors: Wang
authors: Department of Pathology, Tianjin Medical University, Tianjin 300070, China. Electronic address: nannanzhao@yeah.net.
authors: Nan
authors: N
authors: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005455:Fluorescent Antibody Technique; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D051879:Twist-Related Protein 1 / Q000378:metabolism*; D014945:Wound Healing; D023041:Xenograft Model Antitumor Assays
chemical_list: D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1
keywords: Bcl-2; Epithelial–mesenchymal transition; Hypoxia; Twist1; Vasculogenic mimicry