TET1 inhibits gastric cancer growth and metastasis by PTEN demethylation and re-expression
PDF | HTML | Supplementary Files | How to cite
Metrics: PDF 2096 views | HTML 2100 views | ?
Yao-fei Pei1,*, Ran Tao2,*, Jian-fang Li1, Li-ping Su1, Bei-qin Yu1, Xiong-yan Wu1, Min Yan1, Qin-long Gu1, Zheng-gang Zhu1, Bing-ya Liu1
1Shanghai Key Laboratory of Gastric Neoplasms, Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China
2Department of Hepatobiliary-Pancreatic Surgery, Zhejiang Province People’s Hospital, Hangzhou 310014, PR China
*These authors have contributed equally to this work
Bing-ya Liu, email: [email protected]
Keywords: TET1, 5-methylcytosine, 5-hydroxymethylcytosine, gastric cancer, PTEN
Received: February 17, 2016 Accepted: March 31, 2016 Published: April 21, 2016
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.