Hepatocyte nuclear factor-1beta enhances the stemness of hepatocellular carcinoma cells through activation of the Notch pathway

作者：Zhu, Jing-Ni; Jiang, Lu; Jiang, Jing-Hua; Yang, Xue; Li, Xiao-Yong; Zeng, Jian-Xin; Shi, Rong-Yu; Shi, Yang; Pan, Xiao-Rong; Han, Zhi-Peng^*; Wei, Li-Xin^*

来源：Scientific Reports, 2017, 7(1): 4793.

DOI：10.1038/s41598-017-04116-7

• EPITHELIAL-MESENCHYMAL TRANSITION
• EXPRESSION
• CHOLANGIOCARCINOMA
• DIFFERENTIATION
• REVEALS
• CONVERSION
• TISSUE

Hepatocyte nuclear factor-1beta plays an important role in the development and progression of liver cancer. In recent years, the expression of HNF-1 beta has been reported to be associated with risk for a variety of cancers. The purpose of this study is to investigate whether the expression of HNF-1 beta promotes the malignancy of HCC and its mechanism. We retrospectively investigated the expression of HNF-1 beta in 90 patients with hepatocellular carcinoma and found that the high expression of HNF-1 beta indicated poor prognosis. We overexpressed HNF-1 beta in liver cancer cell lines and found the expression of liver progenitor cell markers and stemness were upregulated. The invasion ability and epithelial-mesenchymal transition (EMT)-associated genes were also significantly higher in liver cancer cells overexpressing HNF-1 beta than in the control group. A mechanistic study suggested the activation of the Notch signalling pathway probably plays a key role downstream of HNF-1 beta. More importantly, HNF-1 beta promoted tumourigenesis of HCC cells in vivo. In conclusion, high expression of HNF-1 beta not only promoted the de-differentiation of HCC cells into liver cancer stem cells through activating the Notch pathway but also enhanced the invasive potential of HCC cells and EMT occurrence, which would contribute to the enhancement of cell migration and invasion.

• 出版日期2017-7-6
• 单位山东中医药大学; 福建医科大学; 中国人民解放军第二军医大学