Acid-sensing ion channels contribute to the effect of extracellular acidosis on proliferation and migration of A549 cells

Tumour Biol. 2017 Jun;39(6):1010428317705750. doi: 10.1177/1010428317705750.

Abstract

Acid-sensing ion channels, a proton-gated cation channel, can be activated by low extracellular pH and involved in pathogenesis of some tumors such as glioma and breast cancer. However, the role of acid-sensing ion channels in the growth of lung cancer cell is unclear. In this study, we investigated the expression of acid-sensing ion channels in human lung cancer cell line A549 and their possible role in proliferation and migration of A549 cells. The results show that acid-sensing ion channel 1, acid-sensing ion channel 2, and acid-sensing ion channel 3 are expressed in A549 cells at the messenger RNA and protein levels, and acid-sensing ion channel-like currents were elicited by extracellular acid stimuli. Moreover, we found that acidic extracellular medium or overexpressing acid-sensing ion channel 1a promotes proliferation and migration of A549 cells. In addition psalmotoxin 1, a specific acid-sensing ion channel 1a inhibitor, or acid-sensing ion channel 1a knockdown can abolish the effect of acid stimuli on A549 cells. In addition, acid-sensing ion channels mediate increase of [Ca2+]i induced by low extracellular pH in A549 cells. All these results indicate that acid-sensing ion channel-calcium signal mediate lung cancer cell proliferation and migration induced by extracellular acidosis, and acid-sensing ion channels may serve as a prognostic marker and a therapeutic target for lung cancer.

Keywords: A549 cells; Acid-sensing ion channels; acidosis; lung cancer; migration; proliferation.

MeSH terms

  • A549 Cells
  • Acid Sensing Ion Channels / biosynthesis*
  • Acid Sensing Ion Channels / genetics
  • Acidosis / genetics
  • Acidosis / pathology
  • Biomarkers, Tumor / biosynthesis*
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Prognosis

Substances

  • ASIC1 protein, human
  • ASIC2 protein, human
  • ASIC3 protein, human
  • Acid Sensing Ion Channels
  • Biomarkers, Tumor