PTK7, a Catalytically Inactive Receptor Tyrosine Kinase, Increases Oncogenic Phenotypes in Xenograft Tumors of Esophageal Squamous Cell Carcinoma KYSE-30 Cells.

Won-Sik Shin,Mi-Kyung Park,Seung-Taek Lee,Jae Hoon Kim,Si Won Oh,Ho Lee,Ji-Yun Jang

doi:10.3390/ijms23042391

Abstract

Protein tyrosine kinase 7 (PTK7), a catalytically defective receptor protein tyrosine kinase, is upregulated in tumor tissues and cell lines of esophageal squamous cell carcinoma (ESCC). We showed that PTK7 plays an oncogenic role in various ESCC cell lines. However, its role as an oncogene has not been demonstrated in vivo. Here, we examined the influence of PTK7 on the tumorigenic potential of ESCC KYSE-30 cells, which are known to establish xenograft tumors. Overexpression of PTK7 enhanced the proliferation, adhesion, wound healing, and migration of KYSE-30 cells, and these effects were reversed by the knockdown of PTK7. PTK7 overexpression and knockdown, respectively, increased and decreased the tyrosine phosphorylation of cellular proteins and the phosphorylation of ERK, AKT, and FAK, which are important for cell proliferation, survival, adhesion, and migration. Additionally, PTK7 overexpression and silencing, respectively, increased and decreased the weight, volume, and number of Ki-67-positive proliferating cells in xenograft tumors of KYSE-30 cells. Therefore, we propose that PTK7 plays an important role in the tumorigenesis of ESCC cells in vivo and is a potential therapeutic target for ESCC.

Highlights

Protein tyrosine kinase 7 (PTK7) is a catalytically defective receptor protein tyrosine kinase (RPTK) molecule that contains an extracellular domain with seven immunoglobulin-like loops, a transmembrane domain, and a tyrosine kinase domain lacking catalytic activity [1].Homozygous PTK7 knockout mice are perinatally lethal with severe developmental defects, including defective neural tube closure [2]
We have shown that PTK7 plays a role in enhancing oncogenic properties in TE-6, 9, 10, and 11 esophageal squamous cell carcinoma (ESCC) cells harboring TP53 mutations [24]
We previously showed that PTK7 expression correlates with the promotion of oncogenic properties in several ESCC cells

Summary

Introduction

Homozygous PTK7 knockout mice are perinatally lethal with severe developmental defects, including defective neural tube closure [2]. The PTK7 knockout mice were phenotypically similar to mice and Xenopus with mutations in the planar cell polarity (PCP) genes. PTK7 is genetically linked to the PCP gene Vangl. PTK7 interacts with canonical Wnt signaling pathway proteins, including β-catenin, and activates genes involved in Xenopus development, such as the formation of Spemann’s organizer [3]. PTK7 functions in non-canonical Wnt signaling by switching off canonical Wnt signaling [4]. PTK7 interacts with Wnt5A, a non-canonical Wnt ligand, and induces morphogenetic cell movements in Xenopus [5]. These findings suggest that PTK7 regulates the PCP and canonical and noncanonical Wnt signaling pathways during development

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Discussion

Conclusion