1. Over-expression of ASIC1a promotes proliferation via activation of the β-catenin/LEF-TCF axis and is associated with disease outcome in liver cancer.
- Author
-
Jin C, Yuan FL, Gu YL, Li X, Liu MF, Shen XM, Liu B, and Zhu MQ
- Subjects
- Animals, Apoptosis genetics, Cell Cycle genetics, Cell Line, Tumor, Cell Proliferation, Disease Models, Animal, Gene Expression Regulation, Neoplastic, Gene Knockout Techniques, Heterografts, Humans, Kaplan-Meier Estimate, Liver Neoplasms mortality, Liver Neoplasms pathology, Male, Mice, Models, Biological, Neoplasm Staging, Prognosis, Acid Sensing Ion Channels genetics, Gene Expression, Liver Neoplasms genetics, Liver Neoplasms metabolism, Signal Transduction, TCF Transcription Factors metabolism, beta Catenin metabolism
- Abstract
Acid-sensing ion channels 1a (ASIC1a) has been reported to promote migration and invasion in liver cancer. However, the clinical significance and molecular mechanism of ASIC1a in liver cancer remain unknown. In the study, we found that ASIC1a is frequently up-regulated in liver cancer tissues. The over-expression of ASIC1a is associated with advanced clinical stage and poor prognosis. The pro-proliferative of ASIC1a is pH dependent. Knockout of ASIC1a by CRISPR/CAS9 inhibited liver cancer cell proliferation and tumorigenicity in vitro and in vivo through β-catenin degradation and LEF-TCF inactivation. Our results indicated a potential diagnostic marker and chemotherapeutic target for liver cancer.
- Published
- 2017
- Full Text
- View/download PDF