Abstract | BACKGROUND: METHODS: Levels 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. RESULTS: In 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. CONCLUSIONS: The 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.
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Authors | Xingrong Zheng, Jiaxin Lin, Hewei Wu, Zhishuo Mo, Yunwen Lian, Peipei Wang, Zhaoxia Hu, Zhiliang Gao, Liang Peng, Chan Xie |
Journal | Journal of experimental & clinical cancer research : CR
(J Exp Clin Cancer Res)
Vol. 38
Issue 1
Pg. 475
(Nov 27 2019)
ISSN: 1756-9966 [Electronic] England |
PMID | 31771611
(Publication Type: Journal Article, Retracted Publication)
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Chemical References |
- CTNNB1 protein, human
- FOXG1 protein, human
- Forkhead Transcription Factors
- Nerve Tissue Proteins
- TCF7L2 protein, human
- Transcription Factor 7-Like 2 Protein
- beta Catenin
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Topics |
- Carcinoma, Hepatocellular
(genetics, metabolism, pathology)
- Cell Line, Tumor
- Epithelial-Mesenchymal Transition
- Forkhead Transcription Factors
(biosynthesis, genetics, metabolism)
- Hep G2 Cells
- Humans
- Liver Neoplasms
(genetics, metabolism, pathology)
- Neoplasm Metastasis
- Nerve Tissue Proteins
(biosynthesis, genetics, metabolism)
- Prognosis
- Signal Transduction
- Transcription Factor 7-Like 2 Protein
(metabolism)
- Up-Regulation
- Wnt Signaling Pathway
- beta Catenin
(metabolism)
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