https://scholars.lib.ntu.edu.tw/handle/123456789/473378
標題: | TET1 Suppresses Cancer Invasion by Activating the Tissue Inhibitors of Metalloproteinases | 作者: | Hsu C.-H. Peng K.-L. Kang M.-L. Chen Y.-R. Yang Y.-C. Tsai C.-H. Chu C.-S. YUNG-MING JENG Chen Y.-T. Lin F.-M. Huang H.-D. Lu Y.-Y. Teng Y.-C. Lin S.-T. Lin R.-K. Tang F.-M. Lee S.-B. Hsu H. Yu J.-C. Hsiao P.-W. Juan L.-J. |
公開日期: | 2012 | 卷: | 2 | 期: | 3 | 起(迄)頁: | 568-579 | 來源出版物: | Cell Reports | 摘要: | Tumor suppressor gene silencing through cytosine methylation contributes to cancer formation. Whether DNA demethylation enzymes counteract this oncogenic effect is unknown. Here, we show that TET1, a dioxygenase involved in cytosine demethylation, is downregulated in prostate and breast cancer tissues. TET1 depletion facilitates cell invasion, tumor growth, and cancer metastasis in prostate xenograft models and correlates with poor survival rates in breast cancer patients. Consistently, enforced expression of TET1 reduces cell invasion and breast xenograft tumor formation. Mechanistically, TET1 suppresses cell invasion through its dioxygenase and DNA binding activities. Furthermore, TET1 maintains the expression of tissue inhibitors of metalloproteinase (TIMP) family proteins 2 and 3 by inhibiting their DNA methylation. Concurrent low expression of TET1 and TIMP2 or TIMP3 correlates with advanced node status in clinical samples. Together, these results illustrate a mechanism by which TET1 suppresses tumor development and invasion partly through downregulation of critical gene methylation |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84866908544&doi=10.1016%2fj.celrep.2012.08.030&partnerID=40&md5=8bc73a29973189d3186bfab2694f269b https://scholars.lib.ntu.edu.tw/handle/123456789/473378 |
ISSN: | 2211-1247 | DOI: | 10.1016/j.celrep.2012.08.030 | SDG/關鍵字: | dioxygenase; DNA; protein TET1; tissue inhibitor of metalloproteinase 2; tissue inhibitor of metalloproteinase 3; unclassified drug; animal cell; animal experiment; animal model; animal tissue; article; breast cancer; breast carcinogenesis; cancer growth; cancer inhibition; cancer invasion; cancer patient; cancer survival; cancer tissue; cell invasion; cell migration; controlled study; DNA methylation; down regulation; enzyme activation; human; human cell; human tissue; male; metastasis; mouse; nonhuman; prostate cancer; protein depletion; protein DNA binding; protein expression; tumor xenograft; Animals; Breast Neoplasms; Dioxygenases; DNA Methylation; DNA, Neoplasm; DNA-Binding Proteins; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Prostatic Neoplasms; Proto-Oncogene Proteins; Tissue Inhibitor of Metalloproteinase-2; Tissue Inhibitor of Metalloproteinase-3; Tumor Suppressor Proteins; Citrus maxima |
顯示於: | 病理學科所 |
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