title: Downregulation of spleen tyrosine kinase in hepatocellular carcinoma by promoter CpG island hypermethylation and its potential role in carcinogenesis.
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.
authors.affiliation: Laboratory of Epigenetics, Cancer Research Institute, Brain Korea 21 PLUS, Seoul National University, Seoul, Korea.
authors.forename: So-Hyun
authors.initials: SH
authors.lastname: Shin
authors.affiliation: Departments of Surgery and of Biochemistry and Molecular Biology, USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Pathology, Korea University, Seoul, Korea.
authors.forename: Baek-Hee
authors.initials: BH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Kyung Hee University, Seoul, Korea.
authors.forename: Sun
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hwan Seok
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ja-June
authors.initials: JJ
authors.lastname: Jang
authors.affiliation: 1] Laboratory of Epigenetics, Cancer Research Institute, Brain Korea 21 PLUS, Seoul National University, Seoul, Korea [2] Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
mesh_terms: D000328:Adult; D000368:Aged; D063646:Carcinogenesis; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000209:etiology* / Q000401:mortality; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018899:CpG Islands; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology; D008113:Liver Neoplasms / Q000201:enzymology / Q000209:etiology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D013154:Spleen / Q000201:enzymology; D000072377:Syk Kinase
chemical_list: D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase