title: Vasohibin 2 promotes epithelial-mesenchymal transition in human breast cancer via activation of transforming growth factor β 1 and hypoxia dependent repression of GATA-binding factor 3.
abstract: Vasohibin 2 (VASH2) is identified as an angiogenic factor, and has been implicated in tumor angiogenesis, proliferation and epithelial-mesenchymal transition (EMT). To investigate the EMT role of VASH2 in breast cancer, we overexpressed or knocked down expression of VASH2 in human breast cancer cell lines. We observed that VASH2 induced EMT in vitro and in vivo. The transforming growth factor β1 (TGFβ1) pathway was activated by VASH2, and expression of a dominant negative TGFβ type II receptor could block VASH2-mediated EMT. In clinical breast cancer tissues VASH2 positively correlated with TGFβ1 expression, but negatively correlated with E-cadherin (a marker of EMT) expression. Under hypoxic conditions in vitro or in vivo, we found that down-regulation of estrogen receptor 1 (ESR1) in VASH2 overexpressing ESR1 positive cells suppressed E-cadherin. Correlation coefficient analysis indicated that VASH2 and ESR1 expression were negatively correlated in clinical human breast cancer tissues. Further study revealed that a transcription factor of ESR1, GATA-binding factor 3 (GATA3), was down-regulated by VASH2 under hypoxia or in vivo. These findings suggest that VASH2 drives breast cancer cells to undergo EMT by activation of the TGFβ1 pathway and hypoxia dependent repression GATA3-ESR1 pathway, leading to cancer metastasis.
authors.affiliation: Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Tu
authors.affiliation: Department of Vascular & Herniary Surgery, The People's Hospital of Liaoning Province, PR China.
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Li
authors.affiliation: Invasive Technology Department, Jining No. 1 People's Hospital, PR China.
authors.forename: Xian
authors.initials: X
authors.lastname: Liu
authors.affiliation: Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Lv
authors.affiliation: Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, PR China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Xi
authors.affiliation: Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, PR China.
authors.forename: Zipeng
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, PR China.
authors.forename: Jishu
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Pathology, The First Affiliated Hospital with Nanjing Medical University, PR China.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Song
authors.affiliation: Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, PR China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Chen
authors.affiliation: Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.affiliation: Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, PR China.
authors.forename: Kuirong
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, PR China.
authors.forename: Shui
authors.initials: S
authors.lastname: Wang
authors.affiliation: Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, PR China. Electronic address: gao11@hotmail.com.
authors.forename: Wentao
authors.initials: W
authors.lastname: Gao
authors.affiliation: Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, PR China. Electronic address: miaoyi@njmu.edu.cn.
authors.forename: Yi
authors.initials: Y
authors.lastname: Miao
mesh_terms: D042501:Angiogenic Proteins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D050990:GATA3 Transcription Factor; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D042501:Angiogenic Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D053773:Transforming Growth Factor beta1; C000594357:VASH2 protein, mouse
keywords: Epithelial-mesenchymal transition; GATA-Binding factor 3; Human breast cancer; Transforming growth factor β 1; Vasohibin 2