FAS1 domain protein inhibits VEGF165-induced angiogenesis by targeting the interaction between VEGFR-2 and αvβ3 integrin

Ju Ock Nam, Hye Nam Son, Eunsung Jun, Kiweon Cha, Byung Heon Lee, Rang Woon Park, In-San Kim

Research output: Contribution to journalArticle

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Abstract

It is known that VEGF receptors (VEGFR) and integrins interact with each other to regulate angiogenesis. We reported previously that the fasciclin 1 (FAS1) domain-containing protein, TGFBIp/βig-h3 (TGF-β-induced protein) is an angiogenesis regulator that inhibits both endothelial cell migration and growth via αvβ3 integrin. In an attempt to target the interaction between VEGFR-2 and αvβ3 integrin, we determined whether the FAS1 domain region of TGFBIp/βig-h3 (FAS1 domain protein) can block the interaction between the two receptors, leading to the suppression of angiogenesis. In this study, we showed that FAS1 domain protein inhibits VEGF165-induced endothelial cell proliferation and migration via αvβ3 integrin, resulting in the inhibition of VEGF 165-induced angiogenesis. We also defined a molecular mechanism by which FAS1 domain protein blocks the association between αvβ3 integrin and VEGFR-2, showing that it binds to αvβ3 integrin but not to VEGFR-2. Blocking the association of these major angiogenic receptors with FAS1 domain protein inhibits signaling pathways downstream of VEGFR-2. Collectively, our results indicate that FAS1 domain protein, in addition to its inhibitory effect on αvβ3 integrin-mediated angiogenesis, also inhibits VEGF165-induced angiogenesis. Thus, FAS1 domain protein can be further developed into a potent anticancer drug that targets two principal angiogenic pathways.

Original languageEnglish
Pages (from-to)1010-1020
Number of pages11
JournalMolecular Cancer Research
Volume10
Issue number8
DOIs
Publication statusPublished - 2012 Aug 1
Externally publishedYes

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Vascular Endothelial Growth Factor Receptor
Integrins
Cell Movement
Endothelial Cells
Protein Domains
Cell Proliferation
Growth
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Oncology

Cite this

FAS1 domain protein inhibits VEGF165-induced angiogenesis by targeting the interaction between VEGFR-2 and αvβ3 integrin. / Nam, Ju Ock; Son, Hye Nam; Jun, Eunsung; Cha, Kiweon; Lee, Byung Heon; Park, Rang Woon; Kim, In-San.

In: Molecular Cancer Research, Vol. 10, No. 8, 01.08.2012, p. 1010-1020.

Research output: Contribution to journalArticle

Nam, Ju Ock ; Son, Hye Nam ; Jun, Eunsung ; Cha, Kiweon ; Lee, Byung Heon ; Park, Rang Woon ; Kim, In-San. / FAS1 domain protein inhibits VEGF165-induced angiogenesis by targeting the interaction between VEGFR-2 and αvβ3 integrin. In: Molecular Cancer Research. 2012 ; Vol. 10, No. 8. pp. 1010-1020.
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