標題: TET1 Suppresses Cancer Invasion by Activating the Tissue Inhibitors of Metalloproteinases
作者: Hsu, Chih-Hung
Peng, Kai-Lin
Kang, Ming-Lun
Chen, Yi-Ren
Yang, Yu-Chih
Tsai, Chin-Hsien
Chu, Chi-Shuen
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
生物資訊及系統生物研究所
Institude of Bioinformatics and Systems Biology
公開日期: 1-九月-2012
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: http://dx.doi.org/10.1016/j.celrep.2012.08.030
http://hdl.handle.net/11536/20485
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2012.08.030
期刊: CELL REPORTS
Volume: 2
Issue: 3
起始頁: 568
結束頁: 579
顯示於類別:期刊論文


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  1. 000309716200016.pdf