Over-expression of ASIC1a promotes proliferation via activation of the β-catenin/LEF-TCF axis and is associated with disease outcome in liver cancer

Oncotarget. 2017 Apr 18;8(16):25977-25988. doi: 10.18632/oncotarget.10774.

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.

Keywords: ASIC1a; CRISPR/CAS9; liver cancer; proliferation; β-catenin.

MeSH terms

  • Acid Sensing Ion Channels / genetics*
  • Animals
  • Apoptosis / genetics
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Models, Animal
  • Gene Expression Regulation, Neoplastic
  • Gene Expression*
  • Gene Knockout Techniques
  • Heterografts
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Models, Biological
  • Neoplasm Staging
  • Prognosis
  • Signal Transduction*
  • TCF Transcription Factors / metabolism*
  • beta Catenin / metabolism*

Substances

  • ASIC1 protein, human
  • Acid Sensing Ion Channels
  • TCF Transcription Factors
  • beta Catenin