Article

Journal of Biomedical Science

, Volume 12, Issue 5, pp 803-813

First online:

Epigenetic activation of α4, β2 and β6 integrins involved in cell migration in trichostatin A-treated Hep3B cells

  • Kuen-Tyng LinAffiliated withGraduate Institute of Life Sciences, National Defense Medical Center, National Defense UniversityDivision of Molecular and Genomic Medicine, National Health Research InstitutesAcademia Sinica, Institute of Biomedical Sciences
  • , Shiou-Hwei YehAffiliated withDepartment of Microbiology, College of Medicine, National Taiwan UniversityDivision of Molecular and Genomic Medicine, National Health Research Institutes
  • , Ding-Shinn ChenAffiliated withHepatitis Research Center, Department of Internal Medicine, Hospital and Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University
  • , Pei-Jer ChenAffiliated withHepatitis Research Center, Department of Internal Medicine, Hospital and Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University
  • , Yuh-Shan JouAffiliated withGraduate Institute of Life Sciences, National Defense Medical Center, National Defense UniversityDivision of Molecular and Genomic Medicine, National Health Research InstitutesAcademia Sinica, Institute of Biomedical Sciences Email author 

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Summary

The epigenetic modulation by histone deacetylase (HDAC) inhibitors including trichostatin A (TSA) has been known to block cell proliferation, induce apoptosis and inhibit cell migration in human cancer cells that represents the potential therapeutic agents for cancers and fibrosis. However, more than 55% of Hep3B cells remained alive after our initial study of 100 nM TSA treatment. To further study the epigenetic modulation and the biological function of newly activated genes by HDAC inhibitor involved in HCC progression and metastasis, we profiled 23 integrin genes including 15α and 8β in TSA-treated Hep3B cells. Six integrins including three down-regulated α6, α10, β8 and three significant up-regulated α4, β2, β6 integrins were revealed after semi-quantitative RT-PCR. To confirm the epigenetic modulation and explore their biological functions, we selected the three significantly up-regulated integrins for confirmation of protein up-regulation, hyperacetylated-histones by ChIP assays, and functional inhibition by specific neutralizing antibodies of integrins. Our results indicated that epigenetic modulation in TSA-treated Hep3B cells up-regulated new integrins including α4, β2 and β6 and reduced migration activities by specific neutralizing antibodies to 61.3%, 42.4% and 34.5%, respectively. Our novel findings provided a better understanding of the epigenetic modulation of integrins and suggested that targeting the epigenetic up-regulated integrins to abrogate the migration activity might be a promising strategy to prevent HCC progression.

Keywords

epigenetic hepatocellular carcinoma Hep3B integrins migration