Catalytically inactive receptor tyrosine kinase PTK7 activates FGFR1 independent of FGF

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, f...

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Published in:The FASEB journal 2019-11, Vol.33 (11), p.12960-12971
Main Authors: Shin, Won‐Sik, Lee, Hae Won, Lee, Seung‐Taek
Format: Article
Language:English
Subjects:
ESCC
FGF receptor
oncogenicity
RPTK
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Summary: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). www.fasebj.org
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.201900932R