PMID- 27867016 OWN - NLM STAT- MEDLINE DCOM- 20170905 LR - 20180414 IS - 1872-7980 (Electronic) IS - 0304-3835 (Linking) VI - 388 DP - 2017 Mar 1 TI - Vasohibin 2 promotes epithelial-mesenchymal transition in human breast cancer via activation of transforming growth factor beta 1 and hypoxia dependent repression of GATA-binding factor 3. PG - 187-197 LID - S0304-3835(16)30704-2 [pii] LID - 10.1016/j.canlet.2016.11.016 [doi] AB - 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 beta1 (TGFbeta1) pathway was activated by VASH2, and expression of a dominant negative TGFbeta type II receptor could block VASH2-mediated EMT. In clinical breast cancer tissues VASH2 positively correlated with TGFbeta1 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 TGFbeta1 pathway and hypoxia dependent repression GATA3-ESR1 pathway, leading to cancer metastasis. CI - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved. FAU - Tu, Min AU - Tu M AD - Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, PR China. FAU - Li, Zhanjun AU - Li Z AD - Department of Vascular & Herniary Surgery, The People's Hospital of Liaoning Province, PR China. FAU - Liu, Xian AU - Liu X AD - Invasive Technology Department, Jining No. 1 People's Hospital, PR China. FAU - Lv, Nan AU - Lv N AD - Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, PR China. FAU - Xi, Chunhua AU - Xi C AD - Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, PR China. FAU - Lu, Zipeng AU - Lu Z AD - Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, PR China. FAU - Wei, Jishu AU - Wei J AD - Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, PR China. FAU - Song, Guoxin AU - Song G AD - Department of Pathology, The First Affiliated Hospital with Nanjing Medical University, PR China. FAU - Chen, Jianmin AU - Chen J AD - Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, PR China. FAU - Guo, Feng AU - Guo F AD - Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, PR China. FAU - Jiang, Kuirong AU - Jiang K AD - Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, PR China. FAU - Wang, Shui AU - Wang S AD - Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, PR China. FAU - Gao, Wentao AU - Gao W AD - Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, PR China. Electronic address: gao11@hotmail.com. FAU - Miao, Yi AU - Miao Y AD - Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, PR China. Electronic address: miaoyi@njmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20161117 PL - Ireland TA - Cancer Lett JT - Cancer letters JID - 7600053 RN - 0 (Angiogenic Proteins) RN - 0 (GATA3 Transcription Factor) RN - 0 (GATA3 protein, human) RN - 0 (Transforming Growth Factor beta1) RN - 0 (VASH2 protein, mouse) SB - IM MH - Angiogenic Proteins/*genetics/metabolism MH - Animals MH - Breast Neoplasms/*genetics/pathology MH - Cell Hypoxia MH - Cell Line, Tumor MH - Epithelial-Mesenchymal Transition MH - Female MH - GATA3 Transcription Factor MH - Humans MH - Mice MH - Mice, Nude MH - Transforming Growth Factor beta1/*metabolism OTO - NOTNLM OT - Epithelial-mesenchymal transition OT - GATA-Binding factor 3 OT - Human breast cancer OT - Transforming growth factor beta 1 OT - Vasohibin 2 EDAT- 2016/11/22 06:00 MHDA- 2017/09/07 06:00 CRDT- 2016/11/22 06:00 PHST- 2016/08/29 00:00 [received] PHST- 2016/11/02 00:00 [revised] PHST- 2016/11/10 00:00 [accepted] PHST- 2016/11/22 06:00 [pubmed] PHST- 2017/09/07 06:00 [medline] PHST- 2016/11/22 06:00 [entrez] AID - S0304-3835(16)30704-2 [pii] AID - 10.1016/j.canlet.2016.11.016 [doi] PST - ppublish SO - Cancer Lett. 2017 Mar 1;388:187-197. doi: 10.1016/j.canlet.2016.11.016. Epub 2016 Nov 17.