DOT1L cooperates with the c-Myc-p300 complex to epigenetically derepress CDH1 transcription factors in breast cancer progression

Min-Hyung Cho, Ji-Hye Park, Hee-Joo Choi, Mi-Kyung Park, Hee-Young Won, Yeon-Ji Park, Chang Hoon Lee, Seung-Hyun Oh, Young-Soo Song, Hyun Sung Kim, Young-Ha Oh, Jeong-Yeon Lee () and Gu Kong ()
Additional contact information
Min-Hyung Cho: College of Medicine, Hanyang University
Ji-Hye Park: Institute for Bioengineering and Biopharmaceutical Research (IBBR), Hanyang University
Hee-Joo Choi: College of Medicine, Hanyang University
Mi-Kyung Park: College of Pharmacy, Dongguk University
Hee-Young Won: College of Medicine, Hanyang University
Yeon-Ji Park: College of Medicine, Hanyang University
Chang Hoon Lee: College of Pharmacy, Dongguk University
Seung-Hyun Oh: College of Pharmacy, Gachon University
Young-Soo Song: College of Medicine, Hanyang University
Hyun Sung Kim: College of Medicine, Hanyang University
Young-Ha Oh: College of Medicine, Hanyang University
Jeong-Yeon Lee: Institute for Bioengineering and Biopharmaceutical Research (IBBR), Hanyang University
Gu Kong: College of Medicine, Hanyang University

Nature Communications, 2015, vol. 6, issue 1, 1-14

Abstract: Abstract DOT1L has emerged as an anticancer target for MLL-associated leukaemias; however, its functional role in solid tumours is largely unknown. Here we identify that DOT1L cooperates with c-Myc and p300 acetyltransferase to epigenetically activate epithelial–mesenchymal transition (EMT) regulators in breast cancer progression. DOT1L recognizes SNAIL, ZEB1 and ZEB2 promoters via interacting with the c-Myc-p300 complex and facilitates lysine-79 methylation and acetylation towards histone H3, leading to the dissociation of HDAC1 and DNMT1 in the regions. The upregulation of these EMT regulators by the DOT1L-c-Myc-p300 complex enhances EMT-induced breast cancer stem cell (CSC)-like properties. Furthermore, in vivo orthotopic xenograft models show that DOT1L is required for malignant transformation of breast epithelial cells and breast tumour initiation and metastasis. Clinically, DOT1L expression is associated with poorer survival and aggressiveness of breast cancers. Collectively, we suggest that cooperative effect of DOT1L and c-Myc-p300 is critical for acquisition of aggressive phenotype of breast cancer by promoting EMT/CSC.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms8821 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8821

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms8821

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().