TET1 Suppresses Cancer Invasion by Activating the Tissue Inhibitors of Metalloproteinases
| Autor: | Shinn-Tsuen Lin, Hsien Da Huang, Sung Bau Lee, Huan Ming Hsu, Ming-Lun Kang, Kai-Lin Peng, Chin-Hsien Tsai, Feng Mao Lin, Yi-Ren Chen, Yu-Chih Yang, Yun-Yuh Lu, Pei-Wen Hsiao, Fan-Mei Tang, Chi-Shuen Chu, Li-Jung Juan, Yung-Ming Jeng, Chih-Hung Hsu, Ruo Kai Lin, Yen-Ting Chen, Yu-Ching Teng, Jyh-Cherng Yu |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Tumor suppressor gene Down-Regulation Mice Nude Breast Neoplasms Biology General Biochemistry Genetics and Molecular Biology Dioxygenases Mixed Function Oxygenases Mice chemistry.chemical_compound Downregulation and upregulation Proto-Oncogene Proteins Animals Humans Gene silencing Neoplasm Invasiveness lcsh:QH301-705.5 Tissue Inhibitor of Metalloproteinase-3 Regulation of gene expression 5-Hydroxymethylcytosine Mice Inbred BALB C Tissue Inhibitor of Metalloproteinase-2 Tumor Suppressor Proteins Prostatic Neoplasms DNA Neoplasm Methylation DNA Methylation Molecular biology DNA-Binding Proteins Gene Expression Regulation Neoplastic DNA demethylation chemistry lcsh:Biology (General) DNA methylation Cancer research Female |
| Zdroj: | Cell Reports, Vol 2, Iss 3, Pp 568-579 (2012) |
| ISSN: | 2211-1247 |
| Popis: | SummaryTumor 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. |
| Databáze: | OpenAIRE |
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