Tumor Biology

, Volume 36, Issue 6, pp 4309–4317 | Cite as

Involvement of acid-sensing ion channel 1α in hepatic carcinoma cell migration and invasion

  • Cheng Jin
  • Qing-Hai Ye
  • Feng-Lai Yuan
  • Yuan-Long Gu
  • Jian-Ping Li
  • Ying-Hong Shi
  • Xiao-Min Shen
  • Bo-Liu
  • Zhen-Hai Lin
Research Article


An acidic microenvironment promotes carcinoma cell proliferation and migration. Acid-sensing ion channels (ASICs) are H+, Ca2+, and Na+-gated cation channels that are activated by changes in the extracellular pH, and ASIC1α may be associated with tumor proliferation and migration. Here, we investigated the role of ASIC1α in hepatocellular carcinoma (HCC) migration and invasion. The expression of ASIC1α was examined in 15 paired HCC and adjacent non-tumor tissues by immunohistochemistry. Reverse transcription (RT)-PCR and Western blotting were used to assess ASIC1α messenger RNA (mRNA) and protein expression in the HCC cell line SMMC-7721 cultured in different pH media or transfected with short hairpin RNA (shRNA) against ASIC1α. Cell migration ability was detected by wound healing and Transwell assays. ASIC1α expression was significantly higher in tumor tissues than in non-tumor tissues, and it was higher in HCC with postoperative metastasis than in that without metastasis. ASIC1α mRNA and protein expression was significantly higher in SMMC-7721 cells cultured at pH 6.5 than in those cultured at pH 7.4 and 6.0. shRNA-mediated silencing of ASIC1α significantly downregulated ASIC1α mRNA and protein expression compared with negative control or untransfected cells and inhibited HCC cell migration and invasion. ASIC1α is overexpressed in HCC tissues and associated with advanced clinical stage. A moderately acidic extracellular environment promoted ASIC1α expression, and silencing of ASIC1α expression inhibited the migration and invasion of HCC cells. Suppression of ASIC1α expression by RNAi attenuated the malignant phenotype of HCC cells, suggesting a novel approach for anticancer gene therapy.


Acid-sensing ion channel 1α Hepatic carcinoma Migration Invasion 



This study was supported by grants from the National Natural Science Foundation of China (No. 81301805 and No. 81270011) and the joint research project of hospital management center in Wuxi (No. YGZX1305 and No. YGZX1107). In addition, we are grateful for the guidance of Professor QH Ye.


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Cheng Jin
    • 1
    • 2
  • Qing-Hai Ye
    • 1
  • Feng-Lai Yuan
    • 2
  • Yuan-Long Gu
    • 2
  • Jian-Ping Li
    • 2
  • Ying-Hong Shi
    • 1
  • Xiao-Min Shen
    • 2
  • Bo-Liu
    • 2
  • Zhen-Hai Lin
    • 1
  1. 1.Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer InvasionMinistry of EducationShanghaiChina
  2. 2.Department of Hepatobiliary Pancreatic CenterThe Third Hospital Affiliated to Nantong UniversityWuxiChina

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