https://scholars.lib.ntu.edu.tw/handle/123456789/502681
標題: | H3K9 histone methyltransferase, KMT1E/SETDB1, Cooperates with the SMAD2/3 pathway to suppress lung cancer metastasis | 作者: | 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. |
公開日期: | 2014 | 卷: | 74 | 期: | 24 | 起(迄)頁: | 7333-7343 | 來源出版物: | Cancer Research | 摘要: | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/502681 | ISSN: | 0008-5472 | DOI: | 10.1158/0008-5472.CAN-13-3572 | SDG/關鍵字: | 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 |
顯示於: | 醫學檢驗暨生物技術學系 |
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