Abstract
BackgroundOverexpression of PTK7 has been found in multiple cancers and has been proposed to serve as a prognostic marker for intrahepatic cholangiocarcinoma. Its role in esophageal cancer, however, remains to be clarified. We hypothesize that PTK7 positively regulates tumorigenesis of esophageal cancer.MethodsWe examined PTK7 expression pattern in human esophageal squamous carcinoma by Oncomine expression analysis and by immunohistochemistry (IHC) staining. We knocked down PTK7 in two esophageal squamous cell carcinoma cell lines, TE-5, and TE-9, by siRNA, and evaluated cell proliferation, apoptosis, and migration ofPTK7-defective cells. Expressions of major apoptotic regulators and effectors were also determined by quantitative real-time PCR in PTK7-defective cells. We further overexpressed PTK7 in the cell to evaluate its effects on cell proliferation, apoptosis, and migration.ResultsBoth Oncomine expression and IHC analyses showed that PTK7 is overexpressed in clinical esophageal squamous cell carcinoma tumors. PTK7 siRNA suppressed cell growth and promoted apoptosis of TE-5 and TE-9. PTK7-defective cells further displayed reduced cellular migration that was concomitant with upregulation of E-cadherin. Conversely, overexpression of PTK7 promotes cell proliferation and invasion, while apoptosis of the PTK7-overexpressing cells is repressed. Notably, major apoptotic regulators, such as p53 and caspases, are significantly upregulated in siPTK7 cells.ConclusionsPTK7 plays an oncogenic role in tumorigenesis and metastasis of esophageal squamous carcinoma. PTK7 achieves its oncogenic function in esophageal squamous cell carcinoma partially through the negative regulation of apoptosis.
Highlights
Overexpression of Protein tyrosine kinase-7 (PTK7) has been found in multiple cancers and has been proposed to serve as a prognostic marker for intrahepatic cholangiocarcinoma
IHC analysis showed markedly increased level of PTK7 in the clinical tumors samples of esophageal squamous cell carcinoma than the adjacent normal tissues, and strong staining is predominantly present in the cytoplasm of the disarrayed tumor cells, which is in agreement with its presumable subcellular localization (Fig. 1b)
In the clinical tumor samples we examined, positive or strong positive staining of PTK7is correlated with most tumor samples but not with normal adjacent tissues (Fig. 1b, χ2test, p < 0.001), strongly arguing for an oncogenic role of PTK7 in the tumorigenesis of human esophageal squamous cell carcinoma
Summary
Overexpression of PTK7 has been found in multiple cancers and has been proposed to serve as a prognostic marker for intrahepatic cholangiocarcinoma. Dysregulation of PTK7 has been reported in some cancers, its role in tumorigenesis and oncogenic progression awaits further demonstration. We become motivated to investigate the functions of PTK7 in esophageal squamous carcinomas in the current study. Squamous cell carcinoma and adenocarcinoma are the two major types of esophageal cancer, each of which is associated with different risk factors. Prognosis of esophageal cancer patients is very poor, with the overall 5-year survival rate lingering below 15% in the USA [19]. Most patients die within 1 year of diagnosis, because the disease has already progressed to advanced stages by the time when first symptoms appear. If the cancer could be diagnosed at early stages, the 5-year survival rate would be significantly improved to about 80%. It is imperative to discover new biomarkers to assist with stratification of patients for customized treatment and to minimize the unfavorable side effects or costs that are associated with the current standard chemotherapy or radiotherapy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
