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Sci Rep. 2017 Sep 20;7(1):11994. doi: 10.1038/s41598-017-12344-0.

RORα2 requires LSD1 to enhance tumor progression in breast cancer.

Author information

1
Creative Research Initiatives Center for Chromatin Dynamics, School of Biological Sciences, Seoul National University, Seoul, 151-742, South Korea.
2
Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, 110-744, South Korea.
3
Department of Biological Sciences, Sookmyung Women's University, Seoul, 140-742, South Korea.
4
Severance Biomedical Science Institute, BK21 PLUS project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
5
Creative Research Initiatives Center for Chromatin Dynamics, School of Biological Sciences, Seoul National University, Seoul, 151-742, South Korea. sbaek@snu.ac.kr.

Abstract

Retinoic acid-related orphan receptor α (RORα) regulates diverse physiological processes, including inflammatory responses, lipid metabolism, circadian rhythm, and cancer biology. RORα has four different isoforms which have distinct N-terminal domains but share identical DNA binding domain and ligand binding domain in human. However, lack of specific antibody against each RORα isoform makes biochemical studies on each RORα isoform remain unclear. Here, we generate RORα2-specific antibody and characterize the role of RORα2 in promoting tumor progression in breast cancer. RORα2 requires lysine specific demethylase 1 (LSD1/KDM1A) as a coactivator for transcriptional activation of RORα2 target genes, exemplified by CTNND1. Intriguingly, RORα2 and LSD1 protein levels are dramatically elevated in human breast cancer specimens compared to normal counterparts. Taken together, our studies indicate that LSD1-mediated RORα2 transcriptional activity is important to promote tumor cell migration in human breast cancer as well as breast cancer cell lines. Therefore, our data establish that suppression of LSD1-mediated RORα2 transcriptional activity may be potent therapeutic strategy to attenuate tumor cell migration in human breast cancer.

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