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.
authors.affiliation: Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Seoul, Korea.|Translational Epidemiology Branch, Research Institute, National Cancer Center, Seoul, Korea.|Department of Laboratory Medicine, Center for Diagnostic Oncology, Hospital, National Cancer Center, Seoul, Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Kong
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea.
authors.forename: Kwang-Soo
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea.
authors.forename: Jiewan
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Seoul, Korea.
authors.forename: Min Kyeong
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Seoul, Korea.
authors.forename: Ki Hong
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea.
authors.forename: Je-Yong
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea.
authors.forename: Nuri
authors.initials: N
authors.lastname: Oh
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea.
authors.forename: Ji-In
authors.initials: JI
authors.lastname: Park
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea.
authors.forename: Ji-Hoon
authors.initials: JH
authors.lastname: Park
authors.affiliation: Biomedical Research Center, Asan Institute for Science and Department of Pathology, Asan Medical Center, University of Ulsan, College of Medicine, Ulsan, Korea.
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Heo
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea.
authors.forename: Sung Han
authors.initials: SH
authors.lastname: Shim
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea.
authors.forename: Dong Ryul
authors.initials: DR
authors.lastname: Lee
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul, Korea.
authors.forename: Keun Pil
authors.initials: KP
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea.
authors.forename: Kyung-Soon
authors.initials: KS
authors.lastname: Park
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D054338:Cell Transdifferentiation / Q000502:physiology; D005260:Female; D050990:GATA3 Transcription Factor / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009361:Neoplasm Invasiveness / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: C527883:Elk3 protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors
keywords: ELK3; GATA3; invasion; metastasis; migration