Downregulation of spleen tyrosine kinase in hepatocellular carcinoma by promoter CpG island hypermethylation and its potential role in carcinogenesis

So Hyun Shin, Kwang Ho Lee, Baek Hee Kim, Sun Lee, Hwan Seok Lee, Ja June Jang, Gyeong Hoon Kang

    Research output: Contribution to journalArticlepeer-review

    10 Citations (Scopus)

    Abstract

    Spleen tyrosine kinase (SYK) has predominantly been studied in hematopoietic cells, where it is involved in immunoreceptor-mediated signaling. However, SYK expression has been shown in numerous non-hematopoietic cells, and its downregulation has been shown to be involved in tumor formation and progression. SYK methylation has been demonstrated to identify a subset of hepatocellular carcinoma (HCC) cases with poor prognosis, but little is known regarding the biological role of SYK in HCC. We found that SYK methylation is a common event in HCC, and is inversely associated with its expression. We established stable HCC cell lines with inducible SYK expression vectors, and compared the differential RNA expression profiles of HCC cell lines with or without the induction of SYK. Gene ontology analysis revealed that the SYK-regulated genes were enriched for genes involved in cell adhesion. Accordingly, we found that the induction of SYK expression increased the adhesion of cells to fibronectin and decreased cell migration and invasion, and that cessation of SYK overexpression increased cell migration and invasion. Our findings suggest that SYK is involved in regulating cell to matrix adhesions, and that SYK loss affects the migration, and invasion of HCC cells.

    Original languageEnglish
    Pages (from-to)1396-1405
    Number of pages10
    JournalLaboratory Investigation
    Volume94
    Issue number12
    DOIs
    Publication statusPublished - 2014 Dec 11

    Bibliographical note

    Publisher Copyright:
    © 2014 USCAP, Inc All rights reserved.

    ASJC Scopus subject areas

    • General Medicine

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