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

Autor: Lu Jiang, Xiao-yong Li, Jian-Xin Zeng, Zhipeng Han, Rong-Yu Shi, Xue Yang, Jing-Ni Zhu, Yang Shi, Jinghua Jiang, Lixin Wei, Xiao-Rong Pan
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Pathology
Mice
0302 clinical medicine
Cell Movement
Receptor
Notch1
Mice
Inbred BALB C
Multidisciplinary
Liver Neoplasms
Cell migration
Gene Expression Regulation
Neoplastic
medicine.anatomical_structure
Liver
030220 oncology & carcinogenesis
Hepatocellular carcinoma
Hepatocyte
embryonic structures
Neoplastic Stem Cells
Medicine
Heterografts
Stem cell
Liver cancer
Signal Transduction
medicine.medical_specialty
Carcinoma
Hepatocellular
Epithelial-Mesenchymal Transition
Science
Notch signaling pathway
Mice
Nude
Biology
digestive system
Article
03 medical and health sciences
Cell Line
Tumor
Biomarkers
Tumor
medicine
Animals
Hepatectomy
Humans
Neoplasm Invasiveness
Progenitor cell
Hepatocyte Nuclear Factor 1-beta
Retrospective Studies
Cell Dedifferentiation
medicine.disease
Survival Analysis
030104 developmental biology
Hepatocyte Nuclear Factor 1-Beta
Cancer research
Zdroj: Scientific Reports
Scientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
ISSN: 2045-2322
DOI: 10.1038/s41598-017-04116-7
Popis: Hepatocyte nuclear factor-1beta plays an important role in the development and progression of liver cancer. In recent years, the expression of HNF-1β 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-1β promotes the malignancy of HCC and its mechanism. We retrospectively investigated the expression of HNF-1β in 90 patients with hepatocellular carcinoma and found that the high expression of HNF-1β indicated poor prognosis. We overexpressed HNF-1β 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-1β than in the control group. A mechanistic study suggested the activation of the Notch signalling pathway probably plays a key role downstream of HNF-1β. More importantly, HNF-1β promoted tumourigenesis of HCC cells in vivo. In conclusion, high expression of HNF-1β 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.
Databáze: OpenAIRE
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