RORα2 requires LSD1 to enhance tumor progression in breast cancer

Kyeongkyu Kim; Ji Min Lee; Young Suk Yu; Hyunkyung Kim; Hye Jin Nam; Hyeong Gon Moon; Dong Young Noh; Keun Il Kim; Sungsoon Fang; Sung Hee Baek

doi:10.1038/s41598-017-12344-0

RORα2 requires LSD1 to enhance tumor progression in breast cancer

Kyeongkyu Kim, Ji Min Lee, Young Suk Yu, Hyunkyung Kim, Hye Jin Nam, Hyeong Gon Moon, Dong Young Noh, Keun Il Kim, Sungsoon Fang, Sung Hee Baek

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

10 Citations (Scopus)

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.

Original language	English
Article number	11994
Journal	Scientific reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-12344-0
Publication status	Published - 2017 Dec 1
Externally published	Yes

Bibliographical note

Funding Information:
We thank S. H. Ka for technical help. This work was supported by Creative Research Initiatives Program (Research Center for Chromatin Dynamics, 2009-0081563) to S.H.B.; Basic Science Research Program (NRF-2013R1A2A2A01067617 to K.I.K.; NRF-2014R1A6A3A04057910 to H.K.; NRF-2015R1C1A1A01052195 to S.F) and Korea Mouse Phenotyping Project (2013M3A9D5072550) to S.F; Global Ph.D Fellowship Program (NRF-2011-0008101) to K.K. and (NRF-2012H1A2A1009905) to Y.S.Y. from the National Research Foundation (NRF) grant funded by the Korea government (MSIP); Korea Health Technology R&D Project (HI14C1976) to H.J.N. through the Korea Health Industry Development Institute (KHIDI), funded by the Korea government (MHW).

Publisher Copyright:
© 2017 The Author(s).

ASJC Scopus subject areas

General

UN SDGs

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

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10.1038/s41598-017-12344-0

Cite this

@article{42dc041a9b334b5c8ef375ce6c403966,

title = "RORα2 requires LSD1 to enhance tumor progression in breast cancer",

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.",

author = "Kyeongkyu Kim and Lee, {Ji Min} and Yu, {Young Suk} and Hyunkyung Kim and Nam, {Hye Jin} and Moon, {Hyeong Gon} and Noh, {Dong Young} and Kim, {Keun Il} and Sungsoon Fang and Baek, {Sung Hee}",

note = "Funding Information: We thank S. H. Ka for technical help. This work was supported by Creative Research Initiatives Program (Research Center for Chromatin Dynamics, 2009-0081563) to S.H.B.; Basic Science Research Program (NRF-2013R1A2A2A01067617 to K.I.K.; NRF-2014R1A6A3A04057910 to H.K.; NRF-2015R1C1A1A01052195 to S.F) and Korea Mouse Phenotyping Project (2013M3A9D5072550) to S.F; Global Ph.D Fellowship Program (NRF-2011-0008101) to K.K. and (NRF-2012H1A2A1009905) to Y.S.Y. from the National Research Foundation (NRF) grant funded by the Korea government (MSIP); Korea Health Technology R&D Project (HI14C1976) to H.J.N. through the Korea Health Industry Development Institute (KHIDI), funded by the Korea government (MHW). Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

month = dec,

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doi = "10.1038/s41598-017-12344-0",

language = "English",

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T1 - RORα2 requires LSD1 to enhance tumor progression in breast cancer

AU - Kim, Kyeongkyu

AU - Lee, Ji Min

AU - Yu, Young Suk

AU - Kim, Hyunkyung

AU - Nam, Hye Jin

AU - Moon, Hyeong Gon

AU - Noh, Dong Young

AU - Kim, Keun Il

AU - Fang, Sungsoon

AU - Baek, Sung Hee

N1 - Funding Information: We thank S. H. Ka for technical help. This work was supported by Creative Research Initiatives Program (Research Center for Chromatin Dynamics, 2009-0081563) to S.H.B.; Basic Science Research Program (NRF-2013R1A2A2A01067617 to K.I.K.; NRF-2014R1A6A3A04057910 to H.K.; NRF-2015R1C1A1A01052195 to S.F) and Korea Mouse Phenotyping Project (2013M3A9D5072550) to S.F; Global Ph.D Fellowship Program (NRF-2011-0008101) to K.K. and (NRF-2012H1A2A1009905) to Y.S.Y. from the National Research Foundation (NRF) grant funded by the Korea government (MSIP); Korea Health Technology R&D Project (HI14C1976) to H.J.N. through the Korea Health Industry Development Institute (KHIDI), funded by the Korea government (MHW). Publisher Copyright: © 2017 The Author(s).

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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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DO - 10.1038/s41598-017-12344-0

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SN - 2045-2322

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JO - Scientific reports

JF - Scientific reports

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ER -

RORα2 requires LSD1 to enhance tumor progression in breast cancer

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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