Activation of beta-Catenin by Hypoxia in Hepatocellular Carcinoma Contributes to Enhanced Metastatic Potential and Poor Prognosis

	Activation of beta-Catenin by Hypoxia in Hepatocellular Carcinoma Contributes to Enhanced Metastatic Potential and Poor Prognosis
	Liu, LA; Zhu, XD; Wang, WQ; Shen, YA; Qin, Y; Ren, ZG; Sun, HC; Tang, ZY
刊名	CLINICAL CANCER RESEARCH
	2010
卷号	16 期号:10 页码:2740-2750
通讯作者	Tang, ZY (reprint author), Fudan Univ, Liver Canc Inst, 136 Yi Xue Yuan Rd, Shanghai 200032, Peoples R China.,zytang88@163.com
英文摘要	Purpose: Aberrant activation of beta-catenin contributes to the malignant phenotype in hepatocellular carcinoma (HCC). Hypoxia is also known to promote HCC invasion and metastasis. However, the association between beta-catenin and the proinvasive role of hypoxia remains unclear. We investigated the role of beta-catenin in the proinvasive consequences of hypoxia in HCC. Experimental Design: We established in vitro and in vivo hypoxic models to investigate the expression of beta-catenin in hypoxic HCC cells and its role in hypoxia-induced aggressiveness. The clinical significance of beta-catenin and/or hypoxia-induced factor-1 alpha (HIF-1 alpha) was evaluated using HCC tissue microarrays. Results: Hypoxia induced beta-catenin overexpression and/or intracellular accumulation in four HCC cell lines through downregulating the endogenous degradation machinery, and promoted in vitro invasion and in vivo metastasis of MHCC97 and Hep3B cells. Besides morphologic changes, hypoxic MHCC97 and Hep3B cells exhibited molecular alterations consistent with epithelial-mesenchymal transition, characterized by the loss of epithelial cell markers (E-cadherin and plakoglobin) and upregulation of mesenchymal markers (vimentin and N-cadherin), as well as the increase of matrix metalloproteinase 2. However, silencing beta-catenin in these hypoxic cells reversed epithelial-mesenchymal transition and repressed metastatic potential. Positive expression of beta-catenin in HCC tissue microarray was associated with the expression of HIF-1 alpha (P = 0.034), and coexpression of beta-catenin and HIF-1 alpha in HCC was correlated with shorter overall survival and time to recurrence. Conclusion: beta-Catenin in HCC is activated by hypoxia and contributes to hypoxia-induced metastatic potential. Clin Cancer Res; 16(10); 2740-50. (C) 2010 AACR.
学科主题	Oncology
类目[WOS]	Oncology
关键词[WOS]	EPITHELIAL-MESENCHYMAL TRANSITION ; TUMOR-GROWTH ; PATHWAYS ; PATHOGENESIS ; EXPRESSION ; SURVIVAL ; DISEASE ; CANCER ; CELLS ; MODEL
收录类别	SCI
语种	英语
WOS记录号	WOS:000278597600006
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1061]
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	Liu, LA,Zhu, XD,Wang, WQ,et al. Activation of beta-Catenin by Hypoxia in Hepatocellular Carcinoma Contributes to Enhanced Metastatic Potential and Poor Prognosis[J]. CLINICAL CANCER RESEARCH,2010,16(10):2740-2750.
APA	Liu, LA.,Zhu, XD.,Wang, WQ.,Shen, YA.,Qin, Y.,...&Tang, ZY.(2010).Activation of beta-Catenin by Hypoxia in Hepatocellular Carcinoma Contributes to Enhanced Metastatic Potential and Poor Prognosis.CLINICAL CANCER RESEARCH,16(10),2740-2750.
MLA	Liu, LA,et al."Activation of beta-Catenin by Hypoxia in Hepatocellular Carcinoma Contributes to Enhanced Metastatic Potential and Poor Prognosis".CLINICAL CANCER RESEARCH 16.10(2010):2740-2750.