The ELK3-GATA3 axis orchestrates invasion and metastasis of breast cancer cells in vitro and in vivo
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Sun-Young Kong2,3,4, Kwang-Soo Kim1, Jiewan Kim1, Min Kyeong Kim2, Ki Hong Lee2, Je-Yong Lee1, Nuri Oh1, Ji-In Park1, Ji-Hoon Park1, Sun-Hee Heo5, Sung Han Shim1, Dong Ryul Lee1, Keun Pil Kim6, Kyung-Soon Park1
1Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea
2Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Seoul, Korea
3Translational Epidemiology Branch, Research Institute, National Cancer Center, Seoul, Korea
4Department of Laboratory Medicine, Center for Diagnostic Oncology, Hospital, National Cancer Center, Seoul, Korea
5Biomedical Research Center, Asan Institute for Science and Department of Pathology, Asan Medical Center, University of Ulsan, College of Medicine, Ulsan, Korea
6Department of Life Science, Chung-Ang University, Seoul, Korea
Kyung-Soon Park, email: firstname.lastname@example.org
Keywords: ELK3, GATA3, metastasis, migration, invasion
Received: February 02, 2016 Accepted: August 13, 2016 Published: August 19, 2016
Triple-negative breast cancer is a highly aggressive tumor subtype that lacks effective therapeutic targets. Here, we show that ELK3 is overexpressed in a subset of breast cancers, in particular basal-like and normal-like/claudin-low cell lines. Suppression of ELK3 in MDA-MB-231 cells led to transdifferentiation from an invasive mesenchymal phenotype to a non-invasive epithelial phenotype both in vitro and in vivo. Suppression of ELK3 resulted in extensive changes in genome expression profiles. Among these, GATA3, a master suppressor of metastasis, was epigenetically activated. Also, suppression of GATA3 led to the restoration of migration and invasion. These results suggest that the ELK3-GATA3 axis is a major pathway that promotes metastasis of MDA-MB-231 cells.
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