Sprouty4 deficiency potentiates Ras-independent angiogenic signals and tumor growth

Koji Taniguchi, Takuma Ishizaki, Toranoshin Ayada, Yuki Sugiyama, Yu Wakabayashi, Takashi Sekiya, Ryusuke Nakagawa, Akihiko Yoshimura

研究成果: Article査読

32 被引用数 (Scopus)

抄録

Sprouty proteins have been shown to negatively regulate a variety of receptor tyrosine kinase (RTK) signaling pathways and are considered to be tumor suppressor proteins. The pathophysiological functions of Sproutys in vivo remain to be investigated. In this study, we examined the physiological function of Sprouty4 as an angiogenic regulator, using Sprouty4 knockout (KO) mice and cells.We found that transplanted tumor cells grow much faster in Sprouty4 KO mice than in wild type (WT) mice, which we associate with enhanced neovascularization in the tumors transplanted into Sprouty4 KO mice. Moreover, vascular endothelial growth factor (VEGF)-A-induced angiogenesis and vascular permeability in vivo were enhanced in Sprouty4 KO mice compared with WT mice. Ex vivo angiogenesis, which we induced by VEGF-A, basic fibroblast growth factor (bFGF), and sphingosine-1-phosphate (S1P), was also enhanced in the aortas of Sprouty4 KO mice. We demonstrated that Sprouty4 suppresses Ras-independent VEGF-A and S1P signaling,while it does not affect Ras-dependent VEGF-C signaling. These data indicate that Sprouty4 selectively suppresses Ras-independent angiogenic factor signals and is an important negative regulator of pathophysiological angiogenesis.

本文言語English
ページ(範囲)1648-1654
ページ数7
ジャーナルCancer science
100
9
DOI
出版ステータスPublished - 2009 9

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

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