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

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.

SUBMITTER: Kong SY

PROVIDER: S-EPMC5323143 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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

Kong Sun-Young SY Kim Kwang-Soo KS Kim Jiewan J Kim Min Kyeong MK Lee Ki Hong KH Lee Je-Yong JY Oh Nuri N Park Ji-In JI Park Ji-Hoon JH Heo Sun-Hee SH Shim Sung Han SH Lee Dong Ryul DR Kim Keun Pil KP Park Kyung-Soon KS

Oncotarget 20161001 40

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. ...[more]

PMID: 27556500

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