Regulation of tumor angiogenesis by fastatin, the fourth FAS1 domain of βig-h3, via αvβ3 integrin

Ju Ock Nam, Ha Won Jeong, Byung Heon Lee, Rang Woon Park, In-San Kim

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

We previously reported that the FAS1 domains of βig-h3 bear motifs that mediate endothelial cell adhesion and migration via interactions with αvβ3 integrin and regulate angiogenesis. In the present study, we show that the fourth FAS1 domain, designated fastatin, inhibits endothelial adhesion and migration, not only to βig-h3, but also fibronectin and vitronectin, in a RGD-dependent manner. Fastatin and other FAS1 domains suppress endothelial cell tube formation and in vivo neovascularization in a Matrigel plug assay. The antiangiogenic activity of fastatin is associated with antitumor activity in mouse tumor models. Fastatin additionally induces apoptosis in several cells expressing αvβ3 integrin, including endothelial cells. Binding of fastatin to αvβ3 integrin inhibits phosphorylation of focal adhesion kinase, Raf, extracellular signal-regulated kinase, Akt, and mammalian target of rapamycin. Fastatin is thus the first endogenous angiogenesis regulator identified that inhibits both endothelial cell migration and growth by binding to αvβ3 integrin. Our data suggest that FAS1 domains from all possible forms of the four human FAS1 family proteins are potential endogenous regulators for pathologic angiogenesis. Moreover, FAS1 domains such as fastatin may be developed into drugs for blocking tumor angiogenesis.

Original languageEnglish
Pages (from-to)4153-4161
Number of pages9
JournalCancer Research
Volume65
Issue number10
DOIs
Publication statusPublished - 2005 May 15
Externally publishedYes

Fingerprint

Integrins
Endothelial Cells
Cell Movement
Neoplasms
Pathologic Neovascularization
Vitronectin
Focal Adhesion Protein-Tyrosine Kinases
Extracellular Signal-Regulated MAP Kinases
Sirolimus
Fibronectins
Cell Adhesion
Phosphorylation
Apoptosis
Immunoglobulin Domains
Growth
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Regulation of tumor angiogenesis by fastatin, the fourth FAS1 domain of βig-h3, via αvβ3 integrin. / Nam, Ju Ock; Jeong, Ha Won; Lee, Byung Heon; Park, Rang Woon; Kim, In-San.

In: Cancer Research, Vol. 65, No. 10, 15.05.2005, p. 4153-4161.

Research output: Contribution to journalArticle

Nam, Ju Ock ; Jeong, Ha Won ; Lee, Byung Heon ; Park, Rang Woon ; Kim, In-San. / Regulation of tumor angiogenesis by fastatin, the fourth FAS1 domain of βig-h3, via αvβ3 integrin. In: Cancer Research. 2005 ; Vol. 65, No. 10. pp. 4153-4161.
@article{f20155fbef8440caab6e0cae69e2e6a9,
title = "Regulation of tumor angiogenesis by fastatin, the fourth FAS1 domain of βig-h3, via αvβ3 integrin",
abstract = "We previously reported that the FAS1 domains of βig-h3 bear motifs that mediate endothelial cell adhesion and migration via interactions with αvβ3 integrin and regulate angiogenesis. In the present study, we show that the fourth FAS1 domain, designated fastatin, inhibits endothelial adhesion and migration, not only to βig-h3, but also fibronectin and vitronectin, in a RGD-dependent manner. Fastatin and other FAS1 domains suppress endothelial cell tube formation and in vivo neovascularization in a Matrigel plug assay. The antiangiogenic activity of fastatin is associated with antitumor activity in mouse tumor models. Fastatin additionally induces apoptosis in several cells expressing αvβ3 integrin, including endothelial cells. Binding of fastatin to αvβ3 integrin inhibits phosphorylation of focal adhesion kinase, Raf, extracellular signal-regulated kinase, Akt, and mammalian target of rapamycin. Fastatin is thus the first endogenous angiogenesis regulator identified that inhibits both endothelial cell migration and growth by binding to αvβ3 integrin. Our data suggest that FAS1 domains from all possible forms of the four human FAS1 family proteins are potential endogenous regulators for pathologic angiogenesis. Moreover, FAS1 domains such as fastatin may be developed into drugs for blocking tumor angiogenesis.",
author = "Nam, {Ju Ock} and Jeong, {Ha Won} and Lee, {Byung Heon} and Park, {Rang Woon} and In-San Kim",
year = "2005",
month = "5",
day = "15",
doi = "10.1158/0008-5472.CAN-04-2705",
language = "English",
volume = "65",
pages = "4153--4161",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "10",

}

TY - JOUR

T1 - Regulation of tumor angiogenesis by fastatin, the fourth FAS1 domain of βig-h3, via αvβ3 integrin

AU - Nam, Ju Ock

AU - Jeong, Ha Won

AU - Lee, Byung Heon

AU - Park, Rang Woon

AU - Kim, In-San

PY - 2005/5/15

Y1 - 2005/5/15

N2 - We previously reported that the FAS1 domains of βig-h3 bear motifs that mediate endothelial cell adhesion and migration via interactions with αvβ3 integrin and regulate angiogenesis. In the present study, we show that the fourth FAS1 domain, designated fastatin, inhibits endothelial adhesion and migration, not only to βig-h3, but also fibronectin and vitronectin, in a RGD-dependent manner. Fastatin and other FAS1 domains suppress endothelial cell tube formation and in vivo neovascularization in a Matrigel plug assay. The antiangiogenic activity of fastatin is associated with antitumor activity in mouse tumor models. Fastatin additionally induces apoptosis in several cells expressing αvβ3 integrin, including endothelial cells. Binding of fastatin to αvβ3 integrin inhibits phosphorylation of focal adhesion kinase, Raf, extracellular signal-regulated kinase, Akt, and mammalian target of rapamycin. Fastatin is thus the first endogenous angiogenesis regulator identified that inhibits both endothelial cell migration and growth by binding to αvβ3 integrin. Our data suggest that FAS1 domains from all possible forms of the four human FAS1 family proteins are potential endogenous regulators for pathologic angiogenesis. Moreover, FAS1 domains such as fastatin may be developed into drugs for blocking tumor angiogenesis.

AB - We previously reported that the FAS1 domains of βig-h3 bear motifs that mediate endothelial cell adhesion and migration via interactions with αvβ3 integrin and regulate angiogenesis. In the present study, we show that the fourth FAS1 domain, designated fastatin, inhibits endothelial adhesion and migration, not only to βig-h3, but also fibronectin and vitronectin, in a RGD-dependent manner. Fastatin and other FAS1 domains suppress endothelial cell tube formation and in vivo neovascularization in a Matrigel plug assay. The antiangiogenic activity of fastatin is associated with antitumor activity in mouse tumor models. Fastatin additionally induces apoptosis in several cells expressing αvβ3 integrin, including endothelial cells. Binding of fastatin to αvβ3 integrin inhibits phosphorylation of focal adhesion kinase, Raf, extracellular signal-regulated kinase, Akt, and mammalian target of rapamycin. Fastatin is thus the first endogenous angiogenesis regulator identified that inhibits both endothelial cell migration and growth by binding to αvβ3 integrin. Our data suggest that FAS1 domains from all possible forms of the four human FAS1 family proteins are potential endogenous regulators for pathologic angiogenesis. Moreover, FAS1 domains such as fastatin may be developed into drugs for blocking tumor angiogenesis.

UR - http://www.scopus.com/inward/record.url?scp=20144384004&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20144384004&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-04-2705

DO - 10.1158/0008-5472.CAN-04-2705

M3 - Article

C2 - 15899806

AN - SCOPUS:20144384004

VL - 65

SP - 4153

EP - 4161

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 10

ER -