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; Kyung Soon Park

doi:10.18632/oncotarget.11427

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, Kyung Soon Park^*

^*Corresponding author for this work

Neurological Surgery

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

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.

Original language	English (US)
Pages (from-to)	65137-65146
Number of pages	10
Journal	Oncotarget
Volume	7
Issue number	40
DOIs	https://doi.org/10.18632/oncotarget.11427
State	Published - 2016

Funding

This work was supported by the Korea Science and Engineering Foundation of the Korean government (MOST) (2012M3A9C6050367), and by the Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (2015R1A2A2A01003498, 2015M3A9C6028961). This work was also supported by a National Cancer Center Grant (NCC-1210101).

Keywords

ELK3
GATA3
Invasion
Metastasis
Migration

ASJC Scopus subject areas

Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.18632/oncotarget.11427

Cite this

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title = "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.",

keywords = "ELK3, GATA3, Invasion, Metastasis, Migration",

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T1 - The ELK3-GATA3 axis orchestrates invasion and metastasis of breast cancer cells in vitro and in vivo

AU - Kong, Sun Young

AU - Kim, Kwang Soo

AU - Kim, Jiewan

AU - Kim, Min Kyeong

AU - Lee, Ki Hong

AU - Lee, Je Yong

AU - Oh, Nuri

AU - Park, Ji In

AU - Park, Ji Hoon

AU - Heo, Sun Hee

AU - Shim, Sung Han

AU - Lee, Dong Ryul

AU - Kim, Keun Pil

AU - Park, Kyung Soon

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - ELK3

KW - GATA3

KW - Invasion

KW - Metastasis

KW - Migration

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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