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

doi:10.1016/j.bbrc.2008.04.168

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 journal › Article › peer-review

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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 language	English
Pages (from-to)	793-798
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	371
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2008.04.168
Publication status	Published - 2008 Jul 11

Bibliographical note

Funding Information:
We thank Ae-Ri Ji for technical assistance of confocal microscopy. This work was supported by grants from the Korea Research Foundation (KRF-2004-042-C00086; to STL) and the Korea Science and Engineering Foundation (M10533010001-07N3301-00110; to STL). YGK is a recipient of the National Research Laboratory fund from the Ministry of Science and Technology. W.S.S. and Y.S.M. were recipients of BK21 fellowships supported by the Korean Ministry of Education.

All Science Journal Classification (ASJC) codes

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbrc.2008.04.168

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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.",

author = "Shin, {Won Sik} and Maeng, {Yong Sun} and Jung, {Jae Won} and Min, {Jeong Ki} and Kwon, {Young Guen} and Lee, {Seung Taek}",

note = "Funding Information: We thank Ae-Ri Ji for technical assistance of confocal microscopy. This work was supported by grants from the Korea Research Foundation (KRF-2004-042-C00086; to STL) and the Korea Science and Engineering Foundation (M10533010001-07N3301-00110; to STL). YGK is a recipient of the National Research Laboratory fund from the Ministry of Science and Technology. W.S.S. and Y.S.M. were recipients of BK21 fellowships supported by the Korean Ministry of Education. ",

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AU - Kwon, Young Guen

AU - Lee, Seung Taek

N1 - Funding Information: We thank Ae-Ri Ji for technical assistance of confocal microscopy. This work was supported by grants from the Korea Research Foundation (KRF-2004-042-C00086; to STL) and the Korea Science and Engineering Foundation (M10533010001-07N3301-00110; to STL). YGK is a recipient of the National Research Laboratory fund from the Ministry of Science and Technology. W.S.S. and Y.S.M. were recipients of BK21 fellowships supported by the Korean Ministry of Education.

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N2 - 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.

AB - 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

Abstract

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