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  2. College of Medicine / 醫學院
  3. Clinical Laboratory Sciences and Medical Biotechnology / 醫學檢驗暨生物技術學系所
  4. H3K9 histone methyltransferase, KMT1E/SETDB1, Cooperates with the SMAD2/3 pathway to suppress lung cancer metastasis
 
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H3K9 histone methyltransferase, KMT1E/SETDB1, Cooperates with the SMAD2/3 pathway to suppress lung cancer metastasis

Journal
Cancer Research
Journal Volume
74
Journal Issue
24
Pages
7333-7343
Date Issued
2014
Author(s)
Wu P.-C.
Lu J.-W.
Yang J.-Y.
Lin I.-H.
DA-LIANG OU  
Lin Y.-H.
Chou K.-H.
Huang W.-F.
Wang W.-P.
Huang Y.-L.
CHIUN HSU  
LIANG-IN LIN  
Lin Y.-M.
James Shen C.-K.
Tzeng T.-Y.
DOI
10.1158/0008-5472.CAN-13-3572
URI
https://scholars.lib.ntu.edu.tw/handle/123456789/502681
Abstract
Aberrant histone methylation is a frequent event during tumor development and progression. KMT1E (also known as SETDB1) is a histone H3K9 methyltransferase that contributes to epigenetic silencing of both oncogenes and tumor suppressor genes in cancer cells. In this report, we demonstrate that KMT1E acts as a metastasis suppressor that is strongly downregulated in highly metastatic lung cancer cells. Restoring KMT1E expression in this setting suppressed filopodia formation, migration, and invasive behavior. Conversely, loss of KMT1E in lung cancer cells with limited metastatic potential promoted migration in vitro and restored metastatic prowess in vivo. Mechanistic investigations indicated that KMT1E cooperates with the TGFβ-regulated complex SMAD2/3 to repress metastasis through ANXA2. Together, our findings defined an essential role for the KMT1E/SMAD2/3 repressor complex in TGFβ-mediated lung cancer metastasis. ?2014 AACR.
SDGs

[SDGs]SDG3

Other Subjects
histone methyltransferase; histone methyltransferase H3K9; membrane protein; protein ANXA2; protein KMT1E; protein SETDB1; Smad2 protein; Smad3 protein; unclassified drug; ANXA2 protein, human; lipocortin 2; protein methyltransferase; SETDB1 protein, human; Smad2 protein; SMAD2 protein, human; Smad3 protein; SMAD3 protein, human; actin polymerization; animal experiment; animal model; animal tissue; Article; chromatin immunoprecipitation; controlled study; down regulation; embryo; epigenetics; female; gene overexpression; immunohistochemistry; in vitro study; in vivo study; lung cancer; lung metastasis; metastasis potential; molecular dynamics; mouse; nonhuman; protein analysis; protein expression; protein function; protein modification; signal transduction; transcription regulation; animal; drug screening; gene silencing; genetic epigenesis; genetics; human; lung tumor; metabolism; metastasis; methylation; pathology; promoter region; signal transduction; tumor cell line; zebra fish; Animals; Annexin A2; Cell Line, Tumor; Epigenesis, Genetic; Gene Silencing; Humans; Lung Neoplasms; Methylation; Neoplasm Metastasis; Promoter Regions, Genetic; Protein Methyltransferases; Signal Transduction; Smad2 Protein; Smad3 Protein; Xenograft Model Antitumor Assays; Zebrafish
Type
journal article

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