RETRACTED ARTICLE: Forkhead box (FOX) G1 promotes hepatocellular carcinoma epithelial-Mesenchymal transition by activating Wnt signal through forming T-cell factor-4/Beta-catenin/FOXG1 complex

Journal of Experimental & Clinical Cancer Research

Research

Zhaoxia Hu¹  Zhishuo Mo¹  Xingrong Zheng¹  Peipei Wang¹  Yunwen Lian¹  Hewei Wu¹  Jiaxin Lin¹  Liang Peng²  Zhiliang Gao²  Chan Xie² 

[1] Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, 510630, Guangzhou, Guangdong Province, China;Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, 600# Tianhe Road, 510630, Guangzhou, Guangdong Province, China;Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen University, 510630, Guangzhou, Guangdong Province, China;Guangdong Provincial Key Laboratory of Liver Disease, Guangzhou, China;

关键词: FOXG1;    HCC;    EMT;    Wnt/β-catenin;   

DOI  :  10.1186/s13046-019-1433-3

 received in 2019-08-07, accepted in 2019-10-01,  发布年份 2019

来源: Springer

【 摘 要 】

BackgroundForkhead box G1 (FOXG1) is a member of the Fox transcription factor family involved in regulation of many cancers. However, the role of FOXG1 in hepatocellular carcinogenesisis largely unclear. The present study aimed at examining the biological function and underlying mechanism of FOXG1 on hepatocellular carcinoma (HCC) tumor metastasis as well as its clinical significance.MethodsLevels of FOXG1 were determined by immunohistochemical and real-time PCR analysis in HCC cell lines and human HCC samples. The effect of FOXG1 on cancer cell invasion and metastasis was investigated in vitro and in vivo in either FOXG1-silenced or overexpressing human HCC cell lines. Immunoprecipitation and chromatin immunoprecipitation assays were performed to investigate the interaction of FOXG1, β-catenin, TCF4 and the effect on Wnt target-gene promoters.ResultsIn human HCC, the level of FOXG1 progressively increased from surrounding non tumorous livers to HCC, reaching the highest levels in metastatic HCC. Furthermore, expression levels of FOXG1 directly correlated with cancer cell epithelial-mesenchymal transition (EMT) phenotype. In FOXG1-overexpressing cells, FOXG1 promotes the stabilization and nuclear accumulation of β-catenin by directly binding to β-catenin and it associates with the lymphoid enhancer factor/T cell factor proteins (LEF/TCFs) on Wnt responsive enhancers (WREs) in chromatin.ConclusionsThe results show that FOXG1 plays a key role in mediating cancer cell metastasis through the Wnt/β-catenin pathway in HCC cells and predicts HCC prognosis after surgery. Targeting FOXG1 may provide a new approach for therapeutic treatment in the future.

【 授权许可】

CC BY   
© The Author(s). 2019

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