Targeting TRPV1 on cellular plasticity regulated by Ovol 2 and Zeb 1 in hepatocellular carcinoma

Publication date: October 2019Source: Biomedicine & Pharmacotherapy, Volume 118Author(s): Chengzhi Xie, Guoxing Liu, Min Li, Yu Fang, Ke Qian, Yu Tang, Xiaolong Wu, Xiaohua Lei, Xiaocheng Li, Qiang Liu, Gao Liu, Jiefeng Liu, Yueming Zhang, Zhao Huang, Zecheng Hu, Zhenyu Cao, Jixiong Hu, Shengfu Huang, Dewu Zhong, Jiangsheng HuangAbstractThe landscape of cellular plasticity and sources with relevant niche signals in hepatocellular carcinoma is still obscure. Transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel, is involved in a variety of malignancies and overexpressed in hepatocellular carcinoma (HCC). We have investigated the role of TRPV1 in HCC from different angles by various experimental techniques, such as in vivo and in vitro experiments, and by bioinformatics analysis of data from genetic models induced by diethylnitrosamine (DEN), mice samples and human HCC samples. We find that TRPV1 knockout promotes to hepatocarcinogenesis and deconstructs the portal triad adjacent to tumor border that is contributed by originations of tumor initiating cells and biliary cells. Epithelial to mesenchymal transition (EMT) is involved and transcription factors Ovol2 and Zeb1 coordinated with Sox 10 drive gene expression in the event which is also confirmed by the expression of these proteins in human HCC samples. Treatment with TRPV1 agonist Capsaicin inhibits the growth of HCC cells in xenograft models. Our findings demonstrate that TRPV1 is a potential th...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research