Activation of beta-catenin by hypoxia in hepatocellular carcinoma contributes to enhanced metastatic potential and poor prognosis.

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. 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-1alpha (HIF-1alpha) was evaluated using HCC tissue microarrays. 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-1alpha (P=0.034), and coexpression of beta-catenin and HIF-1alpha in HCC was correlated with shorter overall survival and time to recurrence. beta-Catenin in HCC is activated by hypoxia and contributes to hypoxia-induced metastatic potential.

Liu L ，Zhu XD ，Wang WQ ，Shen Y ，Qin Y ，Ren ZG ，Sun HC ，Tang ZY ... -  《-》

CD24 is a novel predictor for poor prognosis of hepatocellular carcinoma after surgery.

Yang XR ，Xu Y ，Yu B ，Zhou J ，Li JC ，Qiu SJ ，Shi YH ，Wang XY ，Dai Z ，Shi GM ，Wu B ，Wu LM ，Yang GH ，Zhang BH ，Qin WX ，Fan J ... -  《-》

Wnt/β-catenin signaling enhances hypoxia-induced epithelial-mesenchymal transition in hepatocellular carcinoma via crosstalk with hif-1α signaling.

Zhang Q ，Bai X ，Chen W ，Ma T ，Hu Q ，Liang C ，Xie S ，Chen C ，Hu L ，Xu S ，Liang T ... -  《-》

Rac activation is associated with hepatocellular carcinoma metastasis by up-regulation of vascular endothelial growth factor expression.

Lee TK ，Poon RT ，Yuen AP ，Man K ，Yang ZF ，Guan XY ，Fan ST ... -  《CLINICAL CANCER RESEARCH》

Proliferation and migration mediated by Dkk-1/Wnt/beta-catenin cascade in a model of hepatocellular carcinoma cells.

Qin X ，Zhang H ，Zhou X ，Wang C ，Zhang H ，Zhang X ，Ye L ... -  《-》