Soluble PTK7 inhibits tube formation, migration, and invasion of endothelial cells and angiogenesis

Won Sik Shin, Yong Sun Maeng, Jae Won Jung, Jeong Ki Min, Young Guen Kwon, Seung Taek Lee

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Human PTK7 is a defective receptor protein tyrosine kinase and its expression is upregulated in various cancers including colorectal carcinomas. To determine whether PTK7 functions in angiogenesis, we have expressed and purified the extracellular domain of PTK7 (soluble PTK7; sPTK7) as a decoy receptor to counteract the effects of endogenous PTK7. Capillary-like tube formation of human umbilical vascular endothelial cells (HUVECs) was accompanied by modulation in the PTK7 mRNA level. Neutralization of endogenous PTK7 with sPTK7 inhibited vascular endothelial growth factor (VEGF)-induced tube formation, migration, and invasion of HUVECs in a dose-dependent manner. sPTK7 reduced VEGF-induced phosphorylation of focal adhesion kinase (FAK) and paxillin, relocalization of paxillin to focal adhesions, and formation of stress fibers. Moreover, sPTK7 inhibited VEGF-induced angiogenesis in vivo. Knockdown of PTK7 using siRNA also inhibited VEGF-induced tube formation, supporting that sPTK7 specifically blocks function of the endogenous PTK7. These results demonstrate that PTK7 plays an important role not only in tube formation, migration, and invasion of endothelial cells but also in angiogenesis.

Original languageEnglish
Pages (from-to)793-798
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume371
Issue number4
DOIs
Publication statusPublished - 2008 Jul 11

Fingerprint

Endothelial cells
Vascular Endothelial Growth Factor A
Endothelial Cells
Paxillin
Umbilicus
Focal Adhesion Protein-Tyrosine Kinases
Stress Fibers
Phosphorylation
Focal Adhesions
Receptor Protein-Tyrosine Kinases
Small Interfering RNA
Colorectal Neoplasms
Adhesion
Modulation
Messenger RNA
Fibers
Neoplasms

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "Soluble PTK7 inhibits tube formation, migration, and invasion of endothelial cells and angiogenesis",
abstract = "Human PTK7 is a defective receptor protein tyrosine kinase and its expression is upregulated in various cancers including colorectal carcinomas. To determine whether PTK7 functions in angiogenesis, we have expressed and purified the extracellular domain of PTK7 (soluble PTK7; sPTK7) as a decoy receptor to counteract the effects of endogenous PTK7. Capillary-like tube formation of human umbilical vascular endothelial cells (HUVECs) was accompanied by modulation in the PTK7 mRNA level. Neutralization of endogenous PTK7 with sPTK7 inhibited vascular endothelial growth factor (VEGF)-induced tube formation, migration, and invasion of HUVECs in a dose-dependent manner. sPTK7 reduced VEGF-induced phosphorylation of focal adhesion kinase (FAK) and paxillin, relocalization of paxillin to focal adhesions, and formation of stress fibers. Moreover, sPTK7 inhibited VEGF-induced angiogenesis in vivo. Knockdown of PTK7 using siRNA also inhibited VEGF-induced tube formation, supporting that sPTK7 specifically blocks function of the endogenous PTK7. These results demonstrate that PTK7 plays an important role not only in tube formation, migration, and invasion of endothelial cells but also in angiogenesis.",
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Soluble PTK7 inhibits tube formation, migration, and invasion of endothelial cells and angiogenesis. / Shin, Won Sik; Maeng, Yong Sun; Jung, Jae Won; Min, Jeong Ki; Kwon, Young Guen; Lee, Seung Taek.

In: Biochemical and Biophysical Research Communications, Vol. 371, No. 4, 11.07.2008, p. 793-798.

Research output: Contribution to journalArticle

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