High expression of protein tyrosine kinase 7 significantly associates with invasiveness and poor prognosis in intrahepatic cholangiocarcinoma

The incidence, prevalence, and mortality of intrahepatic cholangiocarcinoma (ICC) are increasing worldwide. Protein tyrosine kinase-7 (PTK7) is upregulated in many common human cancers. However, its expression in ICC has not been studied. The present study aimed to explore the underlying mechanism o...

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Bibliographic Details
Published in:PloS one 2014-02, Vol.9 (2), p.e90247-e90247
Main Authors: Jin, Jing, Ryu, Han Suk, Lee, Kyoung Bun, Jang, Ja-June
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Analysis
Animals
Apoptosis
Bile Duct Neoplasms - genetics
Bile Duct Neoplasms - metabolism
Bile Duct Neoplasms - pathology
Bile ducts
Bile Ducts, Intrahepatic - metabolism
Bile Ducts, Intrahepatic - pathology
Biliary tract cancer
Biology
Cell Adhesion Molecules - genetics
Cell Adhesion Molecules - metabolism
Cell Cycle
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Cell growth
Cell Line, Tumor
Cell migration
Cell Movement
Cell proliferation
Cholangiocarcinoma
Cholangiocarcinoma - genetics
Cholangiocarcinoma - metabolism
Cholangiocarcinoma - pathology
Chromosomes
Colorectal cancer
Deoxyribonucleic acid
Digital cameras
DNA
DNA biosynthesis
DNA synthesis
Female
Gene expression
Gene Expression Regulation, Neoplastic
Health aspects
Hospitals
Humans
Invasiveness
Kinases
Male
Medical prognosis
Medicine
Membranes
Mice
Mice, Nude
Middle Aged
Neoplasm Invasiveness
Neoplasm Transplantation
Pathology
Patients
Phenols (Class of compounds)
Polymerase chain reaction
Prognosis
Protein-tyrosine kinase
Proteins
Receptor Protein-Tyrosine Kinases - antagonists & inhibitors
Receptor Protein-Tyrosine Kinases - genetics
Receptor Protein-Tyrosine Kinases - metabolism
Review boards
rho GTP-Binding Proteins - genetics
rho GTP-Binding Proteins - metabolism
RhoA protein
Ribonucleic acid
RNA
RNA, Small Interfering - genetics
RNA, Small Interfering - metabolism
Signal Transduction
siRNA
Surgery
Survival
Synthesis
Tyrosine
Xenografts
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Summary:The incidence, prevalence, and mortality of intrahepatic cholangiocarcinoma (ICC) are increasing worldwide. Protein tyrosine kinase-7 (PTK7) is upregulated in many common human cancers. However, its expression in ICC has not been studied. The present study aimed to explore the underlying mechanism of PTK7 in ICC. The role of PTK7 was studied in vitro by suppressing PTK7 expression in ICC cell lines. The in vivo effect of PTK7 was evaluated using a nude mouse model inoculated with a human ICC cell line. We also examined the role of PTK7 in human ICC samples. Cells with high PTK7 expression exhibited higher proliferation, DNA synthesis, invasion, and migration abilities than did cells with low PTK7 expression. The knockdown of PTK7 with small interfering RNA (siRNA) in high PTK7 expressing cells resulted in impairment of invasion, migration, and DNA synthesis through the regulation of several cell-cycle-related proteins. It also induced cell apoptosis and decreased phospho-RhoA expression. In a xenograft nude mouse model, PTK7 siRNA resulted in a reduction of the tumor size, compared with scrambled siRNA injection. PTK7 expression was higher in human ICC than in the normal bile duct. Patients with low expression of PTK7 had a longer disease-free survival and overall survival than those with high expression. PTK7 expression plays an important role in the invasiveness of ICC cells and leads to a poor prognosis in ICC patients. Thus, PTK7 can be used as a prognostic indicator, and the inhibition of PTK7 expression could be a new therapeutic target for ICC.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0090247