Abstract
Protein tyrosine kinase-7 (PTK7) is a catalytically inactive receptor tyrosine kinase (RTK). PTK7 is upregulated in many common human cancers, including colon cancer, lung cancer, gastric cancer and acute myeloid leukemia. The reason for this up-regulation is not yet known. To explore the functional role of PTK7, the expression of PTK7 in HCT 116 cells was examined using small interference (siRNA)-mediated gene silencing. Following transfection, the siRNA successfully suppressed PTK7 mRNA and protein expression. Knocking down of PTK7 in HCT 116 cells inhibited cell proliferation compared to control groups and induced apoptosis. Furthermore, this apoptosis was characterized by decreased mitochondrial membrane potential and activation of caspase-9 and -10. Addition of a caspase-10 inhibitor totally blocked this apoptosis, suggesting that caspase-10 may play a critical role in PTK7-knockdown-induced apoptosis, downstream of mitochondria. These observations may indicate a role for PTK7 in cell proliferation and cell apoptosis and may provide a potential therapeutic pathway for the treatment of a variety of cancers.
Highlights
Receptor tyrosine kinases (RTKs) compose a class of transmembrane signaling proteins that transmit extracellular signals to the interior of the cell
Protein tyrosine kinase-7 (PTK7), which is known as colon carcinoma kinase-4 (CCK4), is a relatively new and little studied member of the RTK superfamily
After 48 hours, the peak of antiPTK7-PE in HCT 116 transfected with PTK7 siRNA shifted back to the peak of the background control protein, anti-IgG-PE, indicating that the PTK7 expression level in HCT 116 cells transfected with PTK7 siRNA greatly decreased
Summary
Receptor tyrosine kinases (RTKs) compose a class of transmembrane signaling proteins that transmit extracellular signals to the interior of the cell. Protein tyrosine kinase-7 (PTK7), which is known as colon carcinoma kinase-4 (CCK4), is a relatively new and little studied member of the RTK superfamily. It contains an extracellular domain with seven immunoglobulin-like loops, a transmembrane domain, and a catalytically inactive tyrosine kinase domain [2,3]. As a result of an amino acid substitution within the catalytic domain, PTK7 is a pseudokinase without detectable catalytic tyrosine kinase activity [1,4] It was originally identified as a gene-expressed colon cancer-derived cell line, but it is not expressed in human adult colon tissues [2]. The functional role of PTK7 in cell proliferation and apoptosis remains unclear
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