Biomedicine & Pharmacotherapy (Oct 2019)
Targeting TRPV1 on cellular plasticity regulated by Ovol 2 and Zeb 1 in hepatocellular carcinoma
- 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 Huang,
- Fangxiang Wu,
- Jun Wang,
- Masaki Mori,
- Hirofumi Yamamoto,
- Jianxin Wang,
- Xundi Xu
Affiliations
- Chengzhi Xie
- Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The 2ndXiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China; Department of General Surgery, The Second Affiliated Hospital, Hunan University of Chinese Medicine, Changsha, Hunan Province, 410005, China
- Guoxing Liu
- Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The 2ndXiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China
- Min Li
- Department of computer science and technology, School of Information Science and Engineering, Central South University, Changsha, Hunan Province, 410083, China
- Yu Fang
- Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The 2ndXiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China
- Ke Qian
- Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The 2ndXiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China
- Yu Tang
- Department of computer science and technology, School of Information Science and Engineering, Central South University, Changsha, Hunan Province, 410083, China
- Xiaolong Wu
- Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The 2ndXiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China
- Xiaohua Lei
- Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The 2ndXiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China
- Xiaocheng Li
- Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The 2ndXiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China
- Qiang Liu
- Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The 2ndXiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China
- Gao Liu
- Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The 2ndXiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China
- Jiefeng Liu
- Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The 2ndXiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China
- Yueming Zhang
- Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The 2ndXiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China
- Zhao Huang
- Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The 2ndXiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China
- Zecheng Hu
- Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The 2ndXiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China
- Zhenyu Cao
- Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The 2ndXiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China
- Jixiong Hu
- Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The 2ndXiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China
- Shengfu Huang
- Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The 2ndXiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China
- Dewu Zhong
- Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The 2ndXiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China
- Jiangsheng Huang
- Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The 2ndXiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China
- Fangxiang Wu
- Department of computer science and technology, School of Information Science and Engineering, Central South University, Changsha, Hunan Province, 410083, China; Division of Biomedical Engineering, Department of Mechanical Engineering, College of Engineering, University of Saskatchewan, 57 Campus Dr., Saskatoon, SK Canada, Canada
- Jun Wang
- Department of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, TX, 77030, USA
- Masaki Mori
- Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The 2ndXiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China; Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2, Suita City, Osaka, 565-0871, Japan
- Hirofumi Yamamoto
- Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The 2ndXiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China; Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Yamadaoka 2-2, Suita City, Osaka, 565-0871, Japan
- Jianxin Wang
- Department of computer science and technology, School of Information Science and Engineering, Central South University, Changsha, Hunan Province, 410083, China; Corresponding author at: Department of computer science and technology, School of Information Science and Engineering, Central South University, Lushan South Road 293, Changsha, Hunan Province, 410083, China.
- Xundi Xu
- Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The 2ndXiangya Hospital, Central South University, Changsha, Hunan Province, 410011, China; Corresponding author at: Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, The 2nd Xiangya Hospital, Central South University, Renmin Zhong Road 139, Changsha, Hunan Province, 410011, China.
- Journal volume & issue
-
Vol. 118
Abstract
The 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 therapeutic target in human HCC and exerts effects on cellular plasticity with modulation of Ovol2, Zeb1 and Sox10.
