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

Autor: Hwan Seok Lee, Ja June Jang, Gyeong Hoon Kang, Kwang Ho Lee, Sun Lee, So Hyun Shin, Baek Hee Kim
Rok vydání: 2014
Předmět:
Adult
Male
Carcinoma
Hepatocellular
Carcinogenesis
Cell
Down-Regulation
Syk
chemical and pharmacologic phenomena
medicine.disease_cause
environment and public health
Pathology and Forensic Medicine
Downregulation and upregulation
Cell Line
Tumor
hemic and lymphatic diseases
medicine
Humans
Syk Kinase
Neoplasm Invasiveness
Promoter Regions
Genetic
Molecular Biology
Aged
Cell Proliferation
biology
Gene Expression Profiling
Integrin beta1
Liver Neoplasms
Intracellular Signaling Peptides and Proteins
hemic and immune systems
Cell migration
Cell Biology
DNA Methylation
Middle Aged
Protein-Tyrosine Kinases
Molecular biology
Fibronectin
Haematopoiesis
medicine.anatomical_structure
Cell culture
Cancer research
biology.protein
CpG Islands
Female
biological phenomena
cell phenomena
and immunity
Spleen
Zdroj: Laboratory Investigation. 94:1396-1405
ISSN: 0023-6837
Popis: 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.
Databáze: OpenAIRE
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