Oncotarget

Research Papers:

The ELK3-GATA3 axis orchestrates invasion and metastasis of breast cancer cells in vitro and in vivo

Sun-Young Kong, Kwang-Soo Kim, Jiewan Kim, Min Kyeong Kim, Ki Hong Lee, Je-Yong Lee, Nuri Oh, Ji-In Park, Ji-Hoon Park, Sun-Hee Heo, Sung Han Shim, Dong Ryul Lee, Keun Pil Kim and Kyung-Soon Park _

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Oncotarget. 2016; 7:65137-65146. https://doi.org/10.18632/oncotarget.11427

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Abstract

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

Correspondence to:

Kyung-Soon Park, email: [email protected]

Keywords: ELK3, GATA3, metastasis, migration, invasion

Received: February 02, 2016     Accepted: August 13, 2016     Published: August 19, 2016

ABSTRACT

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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