TET1 Suppresses Cancer Invasion by Activating the Tissue Inhibitors of Metalloproteinases

Chih-Hung Hsu, Kai-Lin Peng, Ming-Lun Kang, Yi-Ren Chen, Yu-Chih Yang, Chin-Hsien Tsai, Chi-Shen Chu, Yung-Ming Jeng, Yen-Ting Chen, Feng-Mao Lin, Hsien-Da Huang, Yun-Yuh Lu, Yu-Ching Teng, Shinn-Tsuen Lin, Ruo Kai Lin, Fan-Mei Tang, Sung-Bau Lee, Huan-Ming Hsu, Jyh-Cherng Yu, Pei-Wen HsiaoLi-Jung Juan

研究成果: 雜誌貢獻文章

185 引文 斯高帕斯(Scopus)

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
原文英語
頁(從 - 到)568-579
頁數12
期刊Cell Reports
2
發行號3
DOIs
出版狀態已發佈 - 九月 27 2012

Keywords

  • dioxygenase
  • DNA
  • protein TET1
  • tissue inhibitor of metalloproteinase 2
  • tissue inhibitor of metalloproteinase 3
  • unclassified drug

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Hsu, C-H., Peng, K-L., Kang, M-L., Chen, Y-R., Yang, Y-C., Tsai, C-H., Chu, C-S., Jeng, Y-M., 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-M., Yu, J-C., ... Juan, L-J. (2012). TET1 Suppresses Cancer Invasion by Activating the Tissue Inhibitors of Metalloproteinases. Cell Reports, 2(3), 568-579. https://doi.org/10.1016/j.celrep.2012.08.030