TDP-43 induces EMT and promotes hepatocellular carcinoma metastasis via activating Wnt/beta-catenin signaling pathway

科研成果详情

题名	TDP-43 induces EMT and promotes hepatocellular carcinoma metastasis via activating Wnt/beta-catenin signaling pathway
作者	Guo, Feixia 1,2; Wang, Hongwei 3; Jiang, Min 1; Yang, Qingguo 1; Xiang, Qi 1; Zhou, Hongyin 1; Hu, Xuemei1; Hao, Kaixuan 1; Yang, Jie 1; Cao, HongWen 1; Shen, Zhifa1
发表日期	2020
发表期刊	AMERICAN JOURNAL OF CANCER RESEARCH 影响因子和分区
语种	英语
原始文献类型	Article
关键词	TDP-43 HCC metastasis EMT GSK3 beta Wnt/beta-catenin signaling pathway GSK3β Wnt/β-catenin signaling pathway.
其他关键词	EPITHELIAL-MESENCHYMAL TRANSITION ; NUCLEAR FACTOR TDP-43 ; BETA-CATENIN ; BINDING-PROPERTIES ; CANCER METASTASIS ; RNA ; EXPRESSION ; PROTEIN ; MECHANISMS ; MUTATIONS
摘要	The trans-activation response DNA-binding protein of 43 kDa (TDP-43) is a nuclear protein that has been shown to be involved in the growth and metastasis of breast cancer, neuroblastoma, and melanoma. However, the effect of TDP-43 on hepatocellular carcinoma (HCC) metastasis remains unclear. Here, we demonstrated that TDP-43 was highly upregulated in both clinical samples and cell lines of HCC. Moreover, knockdown and overexpression of TDP-43 efficiently affected the proliferation and metastasis of HCC cells as well as the expression of some proteins associated with epithelial-mesenchymal transition (EMT) and Wnt/beta-catenin signaling pathway. Furthermore, activation of the Wnt/beta-catenin pathway by LiCI restored the effect of TDP-43 knockdown on EMT and HCC cells, whereas inhibition of the Wnt/beta-catenin pathway by XAV939 negated the effect of TDP-43 overexpression. Importantly, we found that TDP-43 protein could interact with GSK3 beta mRNA and regulate the level of GSK3 beta protein translation. Taken together, our findings suggest that TDP-43 may activate the Wnt/beta-catenin pathway by targeting the inhibition of GSK3 beta protein translation, thus inducing the proliferation and metastasis of HCC cells, which supports its potential value as a therapeutic target for the treatment of metastatic HCC.
资助项目	Major Science and Technology Plans for Medicine and Health of Zhejiang, China [WKJ-ZJ1723]; Major Science Technology Projects of Wenzhou, Zhejiang, China [2016Y0852]; Science and Technology projects of Zhejiang, China [LY18H160051]; Science and Technology Projects of Wenzhou, Zhejiang, China [Y20170001]
出版者	E-CENTURY PUBLISHING CORP
出版地	MADISON
ISSN	2156-6976
卷号	10 期号:10 页码:3285-3301
页数	17
WOS类目	Oncology
WOS研究方向	Oncology
WOS记录号	WOS:000583897900013
收录类别	SCIE ; PUBMED
URL	查看原文
PubMed ID	33163270
PMC记录号	PMC7642658
通讯作者地址	[Shen, Zhifa]Wenzhou Med Univ, Inst Funct Nucle Acids & Personalized Canc Theran, Sch Lab Med & Life Sci, Key Lab Lab Med,Minist Educ,Zhejiang Prov Key Lab, Wenzhou 325035, Peoples R China.
引用统计	被引频次：14[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/1388
专题	检验医学院（生命科学学院、生物学实验教学中心）附属第一医院第一临床医学院（信息与工程学院）、附属第一医院_精准医学中心实验室
通讯作者	Shen, Zhifa
作者单位	1.Wenzhou Med Univ, Sch Lab Med & Life Sci, Zhejiang Prov Key Lab Med Genet, Key Lab Lab Med,Minist Educ, Wenzhou 325035, Zhejiang, Peoples R China; 2.Wenzhou Med Univ, Affiliated Hosp 1, Precis Med Ctr Lab, Wenzhou 325000, Zhejiang, Peoples R China; 3.Wenzhou Med Univ, Affiliated Hosp 1, Key Lab Diag & Treatment Severe Hepatopancreat Di, Wenzhou 325000, Zhejiang, Peoples R China
第一作者单位	检验医学院（生命科学学院、生物学实验教学中心）; 第一临床医学院（信息与工程学院）、附属第一医院_精准医学中心实验室
通讯作者单位	温州医科大学
第一作者的第一单位	检验医学院（生命科学学院、生物学实验教学中心）
推荐引用方式 GB/T 7714	Guo, Feixia,Wang, Hongwei,Jiang, Min,et al. TDP-43 induces EMT and promotes hepatocellular carcinoma metastasis via activating Wnt/beta-catenin signaling pathway[J]. AMERICAN JOURNAL OF CANCER RESEARCH,2020,10(10):3285-3301.
APA	Guo, Feixia., Wang, Hongwei., Jiang, Min., Yang, Qingguo., Xiang, Qi., ... & Shen, Zhifa. (2020). TDP-43 induces EMT and promotes hepatocellular carcinoma metastasis via activating Wnt/beta-catenin signaling pathway. AMERICAN JOURNAL OF CANCER RESEARCH, 10(10), 3285-3301.
MLA	Guo, Feixia,et al."TDP-43 induces EMT and promotes hepatocellular carcinoma metastasis via activating Wnt/beta-catenin signaling pathway".AMERICAN JOURNAL OF CANCER RESEARCH 10.10(2020):3285-3301.