期刊
ONCOTARGET
卷 7, 期 40, 页码 65137-65146出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.11427
关键词
ELK3; GATA3; metastasis; migration; invasion
资金
- Korea Science and Engineering Foundation of the Korean government (MOST) [2012M3A9C6050367]
- Priority Research Centers Program through National Research Foundation of Korea (NRF) - Ministry of Education, Science, and Technology [2015R1A2A2A01003498, 2015M3A9C6028961]
- National Cancer Center Grant [NCC-1210101]
- National Research Foundation of Korea [2012M3A9C6050367, 2015R1A2A2A01003498, 2015M3A9C6028961] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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