PTK7 is a novel oncogenic target for esophageal squamous cell carcinoma

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.

Biphasic regulation of tumorigenesis by PTK7 expression level in esophageal squamous cell carcinoma

“…PTK7 knockdown decreased proliferation, survival, wound healing and invasion by inhibiting ERK, JNK, p38, Akt and FAK activation in ESCC TE-10 and TE-11 cells 4 . Overexpression of PTK7 induced cell proliferation and invasion and suppressed apoptosis in ESCC TE-5 and TE-9 cells 24 . Consistently, we found here that overexpression of PTK7 increased proliferation in PTK7-low ESCC TE-5 and TE-14 cells and that PTK7 knockdown decreased it in PTK7-high ESCC TE-6 and TE-10 cells.…”

“…There are several mechanisms by which PTK7 may influence cancer 19 – 21 . For example, PTK7 increases the proliferation, survival, migration, and invasion of cells and wound healing by activating ERK, JNK, p38, and NF-κB signaling pathways, whereas it decreases apoptosis by suppressing the activation of caspase-9 and -10 4 , 19 – 24 . PTK7 also increases angiogenesis through activation of KDR 25 .…”

Bioinformatics Analysis Identifies Protein Tyrosine Kinase 7 (PTK7) as a Potential Prognostic and Therapeutic Biomarker in Stages I to IV Hepatocellular Carcinoma

“…Oncomine database expression studies and immunohistochemistry (IHC) studies have shown that PTK7 is overexpressed esophageal squamous cell carcinoma (ESCC) and may interact with p53 and caspases [20]. Also, PTK7-targeted antibody-drug conjugates reduced the prevalence of tumor-initiating cells and had several anti-tumor effects, including the inhibition of angiogenesis and the stimulation of immune cells [21].…”

Research advances in chimeric antigen receptor-modified T-cell therapy (Review)

“…A number of tumor antigens have been screened to be used for CAR T-cell therapy, among which, our previous study constructed a humanized protein tyrosine kinase 7-CAR through genetic engineering to perform genetic modification of lymphocytes ( Fig. 2 ) ( 39 ).…”