TET1 Suppresses Cancer Invasion by Activating the Tissue Inhibitors of Metalloproteinases
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 tiss...
Main Authors: | , , , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2012-09-01
|
Series: | Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124712002707 |
id |
doaj-d98b7b9806cf4e1eb2311e05786689da |
---|---|
record_format |
Article |
spelling |
doaj-d98b7b9806cf4e1eb2311e05786689da2020-11-24T21:12:03ZengElsevierCell Reports2211-12472012-09-012356857910.1016/j.celrep.2012.08.030TET1 Suppresses Cancer Invasion by Activating the Tissue Inhibitors of MetalloproteinasesChih-Hung Hsu0Kai-Lin Peng1Ming-Lun Kang2Yi-Ren Chen3Yu-Chih Yang4Chin-Hsien Tsai5Chi-Shuen Chu6Yung-Ming Jeng7Yen-Ting Chen8Feng-Mao Lin9Hsien-Da Huang10Yun-Yuh Lu11Yu-Ching Teng12Shinn-Tsuen Lin13Ruo-Kai Lin14Fan-Mei Tang15Sung-Bau Lee16Huan Ming Hsu17Jyh-Cherng Yu18Pei-Wen Hsiao19Li-Jung Juan20Genomics Research Center, Academia Sinica, Taipei 115, Taiwan, ROCGenomics Research Center, Academia Sinica, Taipei 115, Taiwan, ROCGenomics Research Center, Academia Sinica, Taipei 115, Taiwan, ROCAgricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan, ROCAgricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan, ROCAgricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan, ROCGenomics Research Center, Academia Sinica, Taipei 115, Taiwan, ROCGraduate Institute of Pathology, National Taiwan University, Taipei 100, Taiwan, ROCGenomics Research Center, Academia Sinica, Taipei 115, Taiwan, ROCDepartment of Biological Science and Technology, Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu 300, Taiwan, ROCDepartment of Biological Science and Technology, Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu 300, Taiwan, ROCGenomics Research Center, Academia Sinica, Taipei 115, Taiwan, ROCGenomics Research Center, Academia Sinica, Taipei 115, Taiwan, ROCR&D department, GeneTex Asia Ltd, Hsinchu 300, Taiwan, ROCGenomics Research Center, Academia Sinica, Taipei 115, Taiwan, ROCInstitute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan, ROCGenomics Research Center, Academia Sinica, Taipei 115, Taiwan, ROCDivision of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, ROCDivision of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan, ROCAgricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan, ROCGenomics Research Center, Academia Sinica, Taipei 115, Taiwan, ROC 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. http://www.sciencedirect.com/science/article/pii/S2211124712002707 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chih-Hung Hsu Kai-Lin Peng Ming-Lun Kang Yi-Ren Chen Yu-Chih Yang Chin-Hsien Tsai Chi-Shuen 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 Hsiao Li-Jung Juan |
spellingShingle |
Chih-Hung Hsu Kai-Lin Peng Ming-Lun Kang Yi-Ren Chen Yu-Chih Yang Chin-Hsien Tsai Chi-Shuen 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 Hsiao Li-Jung Juan TET1 Suppresses Cancer Invasion by Activating the Tissue Inhibitors of Metalloproteinases Cell Reports |
author_facet |
Chih-Hung Hsu Kai-Lin Peng Ming-Lun Kang Yi-Ren Chen Yu-Chih Yang Chin-Hsien Tsai Chi-Shuen 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 Hsiao Li-Jung Juan |
author_sort |
Chih-Hung Hsu |
title |
TET1 Suppresses Cancer Invasion by Activating the Tissue Inhibitors of Metalloproteinases |
title_short |
TET1 Suppresses Cancer Invasion by Activating the Tissue Inhibitors of Metalloproteinases |
title_full |
TET1 Suppresses Cancer Invasion by Activating the Tissue Inhibitors of Metalloproteinases |
title_fullStr |
TET1 Suppresses Cancer Invasion by Activating the Tissue Inhibitors of Metalloproteinases |
title_full_unstemmed |
TET1 Suppresses Cancer Invasion by Activating the Tissue Inhibitors of Metalloproteinases |
title_sort |
tet1 suppresses cancer invasion by activating the tissue inhibitors of metalloproteinases |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2012-09-01 |
description |
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.
|
url |
http://www.sciencedirect.com/science/article/pii/S2211124712002707 |
work_keys_str_mv |
AT chihhunghsu tet1suppressescancerinvasionbyactivatingthetissueinhibitorsofmetalloproteinases AT kailinpeng tet1suppressescancerinvasionbyactivatingthetissueinhibitorsofmetalloproteinases AT minglunkang tet1suppressescancerinvasionbyactivatingthetissueinhibitorsofmetalloproteinases AT yirenchen tet1suppressescancerinvasionbyactivatingthetissueinhibitorsofmetalloproteinases AT yuchihyang tet1suppressescancerinvasionbyactivatingthetissueinhibitorsofmetalloproteinases AT chinhsientsai tet1suppressescancerinvasionbyactivatingthetissueinhibitorsofmetalloproteinases AT chishuenchu tet1suppressescancerinvasionbyactivatingthetissueinhibitorsofmetalloproteinases AT yungmingjeng tet1suppressescancerinvasionbyactivatingthetissueinhibitorsofmetalloproteinases AT yentingchen tet1suppressescancerinvasionbyactivatingthetissueinhibitorsofmetalloproteinases AT fengmaolin tet1suppressescancerinvasionbyactivatingthetissueinhibitorsofmetalloproteinases AT hsiendahuang tet1suppressescancerinvasionbyactivatingthetissueinhibitorsofmetalloproteinases AT yunyuhlu tet1suppressescancerinvasionbyactivatingthetissueinhibitorsofmetalloproteinases AT yuchingteng tet1suppressescancerinvasionbyactivatingthetissueinhibitorsofmetalloproteinases AT shinntsuenlin tet1suppressescancerinvasionbyactivatingthetissueinhibitorsofmetalloproteinases AT ruokailin tet1suppressescancerinvasionbyactivatingthetissueinhibitorsofmetalloproteinases AT fanmeitang tet1suppressescancerinvasionbyactivatingthetissueinhibitorsofmetalloproteinases AT sungbaulee tet1suppressescancerinvasionbyactivatingthetissueinhibitorsofmetalloproteinases AT huanminghsu tet1suppressescancerinvasionbyactivatingthetissueinhibitorsofmetalloproteinases AT jyhcherngyu tet1suppressescancerinvasionbyactivatingthetissueinhibitorsofmetalloproteinases AT peiwenhsiao tet1suppressescancerinvasionbyactivatingthetissueinhibitorsofmetalloproteinases AT lijungjuan tet1suppressescancerinvasionbyactivatingthetissueinhibitorsofmetalloproteinases |
_version_ |
1716751707422064640 |