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-Hui Kim, Sun Lee, Hwan Seok Lee, Ja June Jang, Gyeong Hoon Kang

Research output: Contribution to journalArticle

4 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 Jan 1

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CpG Islands
Hepatocellular Carcinoma
Carcinogenesis
Down-Regulation
Cell Adhesion
Methylation
Cell Movement
Syk Kinase
Cell-Matrix Junctions
Cell Line
Gene Ontology
Fibronectins
Genes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Downregulation of spleen tyrosine kinase in hepatocellular carcinoma by promoter CpG island hypermethylation and its potential role in carcinogenesis. / Shin, So Hyun; Lee, Kwang Ho; Kim, Baek-Hui; Lee, Sun; Lee, Hwan Seok; Jang, Ja June; Kang, Gyeong Hoon.

In: Laboratory Investigation, Vol. 94, No. 12, 01.01.2014, p. 1396-1405.

Research output: Contribution to journalArticle

Shin, So Hyun ; Lee, Kwang Ho ; Kim, Baek-Hui ; Lee, Sun ; Lee, Hwan Seok ; Jang, Ja June ; Kang, Gyeong Hoon. / Downregulation of spleen tyrosine kinase in hepatocellular carcinoma by promoter CpG island hypermethylation and its potential role in carcinogenesis. In: Laboratory Investigation. 2014 ; Vol. 94, No. 12. pp. 1396-1405.
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