PAQR3 enhances Twist1 degradation to suppress epithelial-mesenchymal transition and metastasis of gastric cancer cells
文献类型：期刊论文
| 作者 | Guo, Weiwei2; You, Xue1,2; Xu, Daqian2; Zhang, Yuxue2; Wang, Zheng2; Man, Kaiyang1,2; Wang, Zhenzhen2; Chen, Yan1,2 |
| 刊名 | CARCINOGENESIS
 |
| 出版日期 | 2016-04-01 |
| 卷号 | 37期号:4页码:397-407 |
| ISSN号 | 0143-3334 |
| DOI | 10.1093/carcin/bgw013 |
| 通讯作者 | Chen, Yan(ychen3@sibs.ac.cn) |
| 英文摘要 | PAQR3, a tumor suppressor, can modulate ubiquitination and degradation of Twist1 that is a key factor for epithelial-mesenchymal transition of tumor cells. Twist1 is indispensable for the inhibitory effect of PAQR3 on metastasis of gastric cancer cells in mice.Twist1 is an essential transcription factor required to initiate epithelial-mesenchymal transition (EMT) and promote tumor metastasis. PAQR3 is a newly found tumor suppressor that is frequently downregulated in many types of human cancers. Downregulation of PAQR3 is associated with accelerated metastasis and poor prognosis of the patients with gastric cancers. In this study, we demonstrate that PAQR3 is actively involved in the degradation of Twist1 and whereby regulates EMT and metastasis of gastric cancer cells. PAQR3 overexpression reduces the protein level but not the mRNA level of Twist1. The protein stability and polyubiquitination of Twist1 are altered by PAQR3. PAQR3 forms a complex with Twist1 and BTRC, an E3 ubiquitin ligase. PAQR3 enhances the interaction between Twist1 and BTRC. Twist1 is mobilized from the nucleus to a proteasome-containing structure in the cytoplasm upon overexpression of PAQR3 and BTRC, which is required for PAQR3-induced degradation of Twist1. The Twist1 box domain of the Twist1 protein is required for the interaction of Twist1 with both PAQR3 and BTRC, indispensable for PAQR3-mediated degradation of Twist1. Both BTRC and Twist1 are required for the inhibitory effects of PAQR3 on migration and EMT phenotype of gastric cancers cells. Importantly, Twist1 is indispensable for the inhibitory effect of PAQR3 on metastasis of gastric cancer cells in vivo. Collectively, these findings not only pinpoint that Twist1 mediates the modulatory function of PAQR3 on EMT and metastasis but also suggest that targeting Twist1 is a promising strategy to control metastasis of tumors with downregulation of PAQR3. |
| 资助项目 | National Natural Science Foundation of China[81390350] ; National Natural Science Foundation of China[81130077] ; National Natural Science Foundation of China[81321062] ; Ministry of Science and Technology of China[2012CB524900] ; Ministry of Science and Technology of China[2013BAI04B03] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000374245300006 |
| 出版者 | OXFORD UNIV PRESS |
| 资助机构 | National Natural Science Foundation of China ; Ministry of Science and Technology of China |
| 源URL | [http://ir.imr.ac.cn/handle/321006/121981]  |
| 专题 | 金属研究所_中国科学院金属研究所 |
| 通讯作者 | Chen, Yan |
| 作者单位 | 1.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China 2.Chinese Acad Sci, Grad Sch Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, 320 Yueyang Rd,New Life Sci Bldg,A2214, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Guo, Weiwei,You, Xue,Xu, Daqian,et al. PAQR3 enhances Twist1 degradation to suppress epithelial-mesenchymal transition and metastasis of gastric cancer cells[J]. CARCINOGENESIS,2016,37(4):397-407. |
| APA | Guo, Weiwei.,You, Xue.,Xu, Daqian.,Zhang, Yuxue.,Wang, Zheng.,...&Chen, Yan.(2016).PAQR3 enhances Twist1 degradation to suppress epithelial-mesenchymal transition and metastasis of gastric cancer cells.CARCINOGENESIS,37(4),397-407. |
| MLA | Guo, Weiwei,et al."PAQR3 enhances Twist1 degradation to suppress epithelial-mesenchymal transition and metastasis of gastric cancer cells".CARCINOGENESIS 37.4(2016):397-407. |
入库方式： OAI收割
来源：金属研究所
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