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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
发布时间:2016-11-28   浏览次数:938

Abstract

Vasohibin 2 (VASH2) is identified as anangiogenic factor, and has been implicated in tumor angiogenesis, proliferationand epithelial-mesenchymal transition (EMT). To investigate the EMT role ofVASH2 in breast cancer, we overexpressed or knocked down expression of VASH2 inhuman breast cancer cell lines. We observed that VASH2 induced EMT in vitro andin vivo. The transforming growth factor β1 (TGFβ1) pathway was activated by VASH2,and expression of a dominant negative TGFβ type II receptor could blockVASH2-mediated EMT. In clinical breast cancer tissues VASH2 positivelycorrelated with TGFβ1 expression, but negatively correlated with E-cadherin (amarker of EMT) expression. Under hypoxic conditions in vitro or in vivo, wefound that down-regulation of estrogen receptor 1 (ESR1) in VASH2overexpressing ESR1 positive cells suppressed E-cadherin. Correlationcoefficient analysis indicated that VASH2 and ESR1 expression were negativelycorrelated in clinical human breast cancer tissues. Further study revealed thata transcription factor of ESR1, GATA-binding factor 3 (GATA3), wasdown-regulated by VASH2 under hypoxia or in vivo. These findings suggest thatVASH2 drives breast cancer cells to undergo EMT by activation of the TGFβ1pathway and hypoxia dependent repression GATA3-ESR1 pathway, leading to cancermetastasis.