PAQR3 enhances Twist1 degradation to suppress epithelial-mesenchymal transition and metastasis of gastric cancer cells

doi:10.1093/carcin/bgw013

	PAQR3 enhances Twist1 degradation to suppress epithelial-mesenchymal transition and metastasis of gastric cancer cells
	Guo, Weiwei 1; You, Xue1,2 ; Xu, Daqian 1; Zhang, Yuxue 1; Wang, Zheng 1; Man, Kaiyang1,2 ; Wang, Zhenzhen 1; Chen, Yan1,2
	2016-04
发表期刊	CARCINOGENESIS (IF:3.3[JCR-2023],3.7[5-Year])
ISSN	0143-3334
卷号	37 期号:4 页码:397-407
发表状态	已发表
DOI	10.1093/carcin/bgw013
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.
收录类别	SCI
语种	英语
资助项目	Ministry of Science and Technology of China[2012CB524900] ; Ministry of Science and Technology of China[2013BAI04B03]
WOS研究方向	Oncology
WOS类目	Oncology
WOS记录号	WOS:000374245300006
出版者	OXFORD UNIV PRESS
WOS关键词	HEPATOCELLULAR-CARCINOMA ; GOLGI-APPARATUS ; MOLECULAR-MECHANISMS ; NUCLEAR-LOCALIZATION ; TUMOR-SUPPRESSOR ; PROSTATE-CANCER ; UP-REGULATION ; RKTG ; PROGRESSION ; PROTEIN
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1883
专题	生命科学与技术学院生命科学与技术学院_特聘教授组_陈雁组生命科学与技术学院_硕士生生命科学与技术学院_博士生
通讯作者	Chen, Yan
作者单位	1.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 2.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China
通讯作者单位	生命科学与技术学院
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.