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

168 引文 (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

指紋

Tissue Inhibitor of Metalloproteinases
Tumors
Dioxygenases
Methylation
Cytosine
Breast Neoplasms
Heterografts
Neoplasms
Down-Regulation
Genes
DNA
Gene Silencing
DNA Methylation
Tumor Suppressor Genes
Prostate
Prostatic Neoplasms
Survival Rate
Tissue
Neoplasm Metastasis
Enzymes

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)

引用此文

Hsu, C-H., Peng, K-L., Kang, M-L., Chen, Y-R., Yang, Y-C., Tsai, C-H., ... 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

TET1 Suppresses Cancer Invasion by Activating the Tissue Inhibitors of Metalloproteinases. / Hsu, Chih-Hung; Peng, Kai-Lin; Kang, Ming-Lun; Chen, Yi-Ren; Yang, Yu-Chih; Tsai, Chin-Hsien; Chu, Chi-Shen; Jeng, Yung-Ming; Chen, Yen-Ting; Lin, Feng-Mao; Huang, Hsien-Da; Lu, Yun-Yuh; Teng, Yu-Ching; Lin, Shinn-Tsuen; Lin, Ruo Kai; Tang, Fan-Mei; Lee, Sung-Bau; Hsu, Huan-Ming; Yu, Jyh-Cherng; Hsiao, Pei-Wen; Juan, Li-Jung.

於: Cell Reports, 卷 2, 編號 3, 27.09.2012, p. 568-579.

研究成果: 雜誌貢獻文章

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, RK, Tang, F-M, Lee, S-B, Hsu, H-M, Yu, J-C, Hsiao, P-W & Juan, L-J 2012, 'TET1 Suppresses Cancer Invasion by Activating the Tissue Inhibitors of Metalloproteinases', Cell Reports, 卷 2, 編號 3, 頁 568-579. https://doi.org/10.1016/j.celrep.2012.08.030
Hsu, Chih-Hung ; Peng, Kai-Lin ; Kang, Ming-Lun ; Chen, Yi-Ren ; Yang, Yu-Chih ; Tsai, Chin-Hsien ; Chu, Chi-Shen ; Jeng, Yung-Ming ; Chen, Yen-Ting ; Lin, Feng-Mao ; Huang, Hsien-Da ; Lu, Yun-Yuh ; Teng, Yu-Ching ; Lin, Shinn-Tsuen ; Lin, Ruo Kai ; Tang, Fan-Mei ; Lee, Sung-Bau ; Hsu, Huan-Ming ; Yu, Jyh-Cherng ; Hsiao, Pei-Wen ; Juan, Li-Jung. / TET1 Suppresses Cancer Invasion by Activating the Tissue Inhibitors of Metalloproteinases. 於: Cell Reports. 2012 ; 卷 2, 編號 3. 頁 568-579.
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abstract = "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",
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AU - Lee, Sung-Bau

AU - Hsu, Huan-Ming

AU - Yu, Jyh-Cherng

AU - Hsiao, Pei-Wen

AU - Juan, Li-Jung

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