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TET1 inhibits gastric cancer growth and metastasis by PTEN demethylation and re-expression
Ten-Eleven Translocation 1 (TET1) is a member of ten eleven translocation enzymes, which convert 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC). TET1 can promote CpG islands demethylation in specific genes and often absent in various cancers. Herein, we found that TET1 expression and 5-h...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058759/ https://www.ncbi.nlm.nih.gov/pubmed/27121319 http://dx.doi.org/10.18632/oncotarget.8900 |
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author | Pei, Yao-fei Tao, Ran Li, Jian-fang Su, Li-ping Yu, Bei-qin Wu, Xiong-yan Yan, Min Gu, Qin-long Zhu, Zheng-gang Liu, Bing-ya |
author_facet | Pei, Yao-fei Tao, Ran Li, Jian-fang Su, Li-ping Yu, Bei-qin Wu, Xiong-yan Yan, Min Gu, Qin-long Zhu, Zheng-gang Liu, Bing-ya |
author_sort | Pei, Yao-fei |
collection | PubMed |
description | Ten-Eleven Translocation 1 (TET1) is a member of ten eleven translocation enzymes, which convert 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC). TET1 can promote CpG islands demethylation in specific genes and often absent in various cancers. Herein, we found that TET1 expression and 5-hmC content were low in gastric tumors compared to its adjacent non-tumor tissues. Cell proliferation, migration and invasion were enhanced upon TET1 knockdown in gastric cancer cells in vitro. This phenomenon was confirmed by an animal xeongraft model. We also found that TET1 directly binds to the promoter region of PTEN and activates its transcription through demethylation of CpG islands. TET1 knockdown activated AKT and FAK pathways, which were suppressed by PTEN. The activation of AKT and FAK facilitated tumor migration, invasion and accelerated cell growth. In conclusion, we found a novel mechanism that TET1 suppresses tumor cell growth, migration and invasion through demethylation of CpG island in PTEN promoter by increasing 5-hmC content. The re-expressed PTEN subsequently down regulates AKT and FAK activity. |
format | Online Article Text |
id | pubmed-5058759 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-50587592016-10-15 TET1 inhibits gastric cancer growth and metastasis by PTEN demethylation and re-expression Pei, Yao-fei Tao, Ran Li, Jian-fang Su, Li-ping Yu, Bei-qin Wu, Xiong-yan Yan, Min Gu, Qin-long Zhu, Zheng-gang Liu, Bing-ya Oncotarget Research Paper Ten-Eleven Translocation 1 (TET1) is a member of ten eleven translocation enzymes, which convert 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC). TET1 can promote CpG islands demethylation in specific genes and often absent in various cancers. Herein, we found that TET1 expression and 5-hmC content were low in gastric tumors compared to its adjacent non-tumor tissues. Cell proliferation, migration and invasion were enhanced upon TET1 knockdown in gastric cancer cells in vitro. This phenomenon was confirmed by an animal xeongraft model. We also found that TET1 directly binds to the promoter region of PTEN and activates its transcription through demethylation of CpG islands. TET1 knockdown activated AKT and FAK pathways, which were suppressed by PTEN. The activation of AKT and FAK facilitated tumor migration, invasion and accelerated cell growth. In conclusion, we found a novel mechanism that TET1 suppresses tumor cell growth, migration and invasion through demethylation of CpG island in PTEN promoter by increasing 5-hmC content. The re-expressed PTEN subsequently down regulates AKT and FAK activity. Impact Journals LLC 2016-04-21 /pmc/articles/PMC5058759/ /pubmed/27121319 http://dx.doi.org/10.18632/oncotarget.8900 Text en Copyright: © 2016 Pei et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Pei, Yao-fei Tao, Ran Li, Jian-fang Su, Li-ping Yu, Bei-qin Wu, Xiong-yan Yan, Min Gu, Qin-long Zhu, Zheng-gang Liu, Bing-ya TET1 inhibits gastric cancer growth and metastasis by PTEN demethylation and re-expression |
title | TET1 inhibits gastric cancer growth and metastasis by PTEN demethylation and re-expression |
title_full | TET1 inhibits gastric cancer growth and metastasis by PTEN demethylation and re-expression |
title_fullStr | TET1 inhibits gastric cancer growth and metastasis by PTEN demethylation and re-expression |
title_full_unstemmed | TET1 inhibits gastric cancer growth and metastasis by PTEN demethylation and re-expression |
title_short | TET1 inhibits gastric cancer growth and metastasis by PTEN demethylation and re-expression |
title_sort | tet1 inhibits gastric cancer growth and metastasis by pten demethylation and re-expression |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058759/ https://www.ncbi.nlm.nih.gov/pubmed/27121319 http://dx.doi.org/10.18632/oncotarget.8900 |
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