Metadherin Promotes Hepatocellular Carcinoma Metastasis through Induction of Epithelial-Mesenchymal Transition

	Metadherin Promotes Hepatocellular Carcinoma Metastasis through Induction of Epithelial-Mesenchymal Transition
	Zhu, K; Dai, Z; Pan, Q; Wang, Z; Yang, GH; Yu, L; Ding, ZB; Shi, GM; Ke, AW; Yang, XR
刊名	CLINICAL CANCER RESEARCH
	2011
卷号	17 期号:23 页码:7294-7302
通讯作者	Zhou, J (reprint author), Fudan Univ, Zhong Shan Hosp, Liver Canc Inst, Shanghai 200032, Peoples R China.,zhou.jian@zs-hospital.sh.cn
英文摘要	Purpose: To investigate the expression of metadherin (MTDH) for its prognostic value in hepatocellular carcinoma (HCC) and its role in promoting HCC metastasis. Experimental Design: This study employed a tissue microarray containing samples from 323 HCC patients to examine the expression of MTDH and its correlation with other clinicopathologic characteristics. The role of MTDH in the regulation of HCC metastasis was investigated both in vitro and in vivo using short hairpin RNA (shRNA)-mediated downregulation of MTDH in HCC cell lines with various metastatic potentials. Results: The expression of MTDH was markedly higher in HCC tumors than in normal liver tissue. Particularly high MTDH expression was observed in tumors with microvascular invasion, pathologic satellites, poor differentiation, or tumor-node-metastasis stages II to III. Furthermore, the clinical outcome was consistently poorer for the MTDH(high) group than for the MTDH(low) group in the 1-, 3-, and 5-year overall survival (OS) rates and in the 1-, 3-, 5-year cumulative recurrence rates. In a nude mice model, the shRNA-mediated downregulation of MTDH resulted in a reduced migratory capacity in HCC cell lines, as well as a reduction in pulmonary and abdominal metastasis. Furthermore, we found that the expression level of MTDH correlated with four epithelial-mesenchymal transition (EMT) markers. Knockdown of MTDH expression in HCC cell lines resulted in downregulation of N-cadherin and snail, upregulation of E-cadherin, and translocation of beta-catenin. Conclusions: MTDH may promote HCC metastasis through the induction of EMT process and may be a candidate biomarker for prognosis as well as a target for therapy. Clin Cancer Res; 17(23); 7294-302. (C)2011 AACR.
学科主题	Oncology
类目[WOS]	Oncology
关键词[WOS]	ASTROCYTE ELEVATED GENE-1 ; TRANSCRIPTION FACTOR SNAIL ; E-CADHERIN ; POOR-PROGNOSIS ; TUMOR PROGRESSION ; BREAST-CANCER ; BETA-CATENIN ; N-CADHERIN ; EXPRESSION ; ACTIVATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000298133600012
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/883]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Zhu, K,Dai, Z,Pan, Q,et al. Metadherin Promotes Hepatocellular Carcinoma Metastasis through Induction of Epithelial-Mesenchymal Transition[J]. CLINICAL CANCER RESEARCH,2011,17(23):7294-7302.
APA	Zhu, K.,Dai, Z.,Pan, Q.,Wang, Z.,Yang, GH.,...&Zhou, J.(2011).Metadherin Promotes Hepatocellular Carcinoma Metastasis through Induction of Epithelial-Mesenchymal Transition.CLINICAL CANCER RESEARCH,17(23),7294-7302.
MLA	Zhu, K,et al."Metadherin Promotes Hepatocellular Carcinoma Metastasis through Induction of Epithelial-Mesenchymal Transition".CLINICAL CANCER RESEARCH 17.23(2011):7294-7302.