Catalytically inactive receptor tyrosine kinase PTK7 activates FGFR1 independent of FGF

Won Sik Shin, Hae Won Lee, Seung Taek Lee

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10 Citations (Scopus)


Protein tyrosine kinase 7 (PTK7), a catalytically defective receptor protein tyrosine kinase (RPTK), plays an oncogenic role by activating an unidentified TKI-258 (dovitinib)-sensitive RPTK in esophageal squamous cell carcinoma (ESCC) cells. Here, we demonstrate that among TKI-258-sensitive RPTKs, fibroblast growth factor receptor (FGFR) 1 is significantly up-regulated in ESCC tissues and cell lines. We show that PTK7 colocalizes with FGFR1 and binds it via its extracellular domain in human embryonic kidney 293 and ESCC TE-10 cells. PTK7 knockdown not only reduced ligand-free and fibroblast growth factor (FGF)-induced phosphorylation of FGFR1 but also the interaction of signaling adaptor proteins with FGFR1 and activation of downstream signaling proteins in TE-10 cells. In addition, PTK7 knockdown reduced FGF-induced oncogenic phenotypes including proliferation, anchorage-independent colony formation, wound healing, and invasion in ESCC cells. Taken together, our data demonstrate that PTK7 binds and activates FGFR1 independent of FGF and thus increases oncogenicity of PTK7- and FGFR1-positive cancers such as ESCC.—Shin, W.-S., Lee, H. W., Lee, S.-T. Catalytically inactive receptor tyrosine kinase PTK7 activates FGFR1 independent of FGF. FASEB J. 33, 12960–12971 (2019).

Original languageEnglish
Pages (from-to)12960-12971
Number of pages12
JournalFASEB Journal
Issue number11
Publication statusPublished - 2019 Nov 1

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation of Korea (2016R1A2B4007904 and 2019M3A9A8065054 to S.‐T.L. and 2019R1C1C1005027 to W.‐S.S.). W.‐S.S. is a recipient of the Yonsei Frontier Laboratory Young Researcher Supporting Program of the Yonsei University Research Fund. The authors declare no conflicts of interest.

Publisher Copyright:

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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