Research Papers:

Catalytically defective receptor protein tyrosine kinase PTK7 enhances invasive phenotype by inducing MMP-9 through activation of AP-1 and NF-κB in esophageal squamous cell carcinoma cells

Won-Sik Shin, Yuri Hong, Hae Won Lee and Seung-Taek Lee _

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Oncotarget. 2016; 7:73242-73256. https://doi.org/10.18632/oncotarget.12303

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Won-Sik Shin1, Yuri Hong1, Hae Won Lee2, Seung-Taek Lee1

1Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea

2Department of Thoracic Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea

Correspondence to:

Seung-Taek Lee, email: [email protected]

Keywords: PTK7, MMP-9, NF-κB, AP-1, esophageal squamous cell carcinoma (ESCC)

Received: June 04, 2016     Accepted: September 21, 2016     Published: September 28, 2016


Protein tyrosine kinase 7 (PTK7), a member of the catalytically defective receptor protein tyrosine kinase family, is upregulated in various cancers including esophageal squamous cell carcinoma (ESCC). Here, we have explored the molecular mechanism of PTK7-dependent invasiveness in ESCC cells. PTK7 knockdown reduced gelatin degradation and MMP-9 secretion in cultures of ESCC TE-10 cells, and showed reduced levels of MMP9 mRNA using real-time RT-PCR and luciferase reporter assays. PTK7 knockdown decreased not only phosphorylation of NF-κB, IκB, ERK, and JNK, but also nuclear localization of NF-κB and AP-1 consisting of c-Fos and c-Jun. Activation of AP-1 and NF-κB requires PTK7-mediated activation of tyrosine kinases, including Src. In addition, NF-κB activation by PTK7 involves the PI3K/Akt signaling pathway. PTK7-mediated upregulation of MMP9 was also observed in other ESCC cell lines and in three-dimensional cultures of TE-10 cells. Moreover, MMP-9 expression positively correlated with PTK7 expression in ESCC tumor tissue. These findings demonstrate that PTK7 upregulates MMP9 through activation of AP-1 and NF-κB and, thus increases invasive properties of ESCC cells.

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