title: BRD4 inhibitor inhibits colorectal cancer growth and metastasis.
abstract: Post-translational modifications have been identified to be of great importance in cancers and lysine acetylation, which can attract the multifunctional transcription factor BRD4, has been identified as a potential therapeutic target. In this paper, we identify that BRD4 has an important role in colorectal cancer; and that its inhibition substantially wipes out tumor cells. Treatment with inhibitor MS417 potently affects cancer cells, although such effects were not always outright necrosis or apoptosis. We report that BRD4 inhibition also limits distal metastasis by regulating several key proteins in the progression of epithelial-to-mesenchymal transition (EMT). This effect of BRD4 inhibitor is demonstrated via liver metastasis in animal model as well as migration and invasion experiments in vitro. Together, our results demonstrate a new application of BRD4 inhibitor that may be of clinical use by virtue of its ability to limit metastasis while also being tumorcidal.
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Road, Guangzhou 510515, China. drhuyuan@gmail.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Road, Guangzhou 510515, China. zhoujieqiong2008@sina.com.
authors.forename: Jieqiong
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. fei.ye@mssm.edu.
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.affiliation: Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. huabao.xiong@mssm.edu.
authors.forename: Huabao
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. liang.peng@mssm.edu.
authors.forename: Liang
authors.initials: L
authors.lastname: Peng
authors.affiliation: College of Arts and Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA. zihanz@live.unc.edu.
authors.forename: Zihan
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. feihong.xu@mssm.edu.
authors.forename: Feihong
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. miao.cui@mssm.edu.
authors.forename: Miao
authors.initials: M
authors.lastname: Cui
authors.affiliation: Departments of Medicine Bioinformatics Core, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. chengguo.wei@mssm.edu.
authors.forename: Chengguo
authors.initials: C
authors.lastname: Wei
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Road, Guangzhou 510515, China. sunwingwxy@163.com.
authors.forename: Xinying
authors.initials: X
authors.lastname: Wang
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Road, Guangzhou 510515, China. wangzq815@gmail.com.
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. hongfa.zhu@mountsinai.org.
authors.forename: Hongfa
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Departments of Pathology, Urology, NYU Cancer Institute, New York Harbor Healthcare System, New York University, School of Medicine, New York, NY 10010, USA. Peng.Lee@nyumc.org.
authors.forename: Peng
authors.initials: P
authors.lastname: Lee
authors.affiliation: Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. ming-ming.zhou@mssm.edu.
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Road, Guangzhou 510515, China. drjiang@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. david.zhang@mssm.edu.
authors.forename: David Y
authors.initials: DY
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D003984:Dibenzazepines / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D055815:Young Adult; D000092468:Bromodomain Containing Proteins
chemical_list: D018797:Cell Cycle Proteins; D003984:Dibenzazepines; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins