Overexpression of sprouty 2 inhibits HGF/SF-mediated cell growth, invasion, migration, and cytokinesis

被引：110

作者：

Lee, CC ^{[1
]}

Putnam, AJ ^{[1
]}

Miranti, CK ^{[1
]}

Gustafson, M ^{[1
]}

Wang, LM ^{[1
]}

Woude, GFV ^{[1
]}

Gao, CF ^{[1
]}

机构：

[1] Van Andel Res Inst, Grand Rapids, MI 49503 USA

来源：

ONCOGENE | 2004年 / 23卷 / 30期

关键词：

sprouty; hepatocyte growth factor/scatter factor; met; signaling; invasion; migration;

D O I：

10.1038/sj.onc.1207646

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A strict regulation of hepatocyte growth factor/scatter factor (HGF/SF)-Met signaling is essential for its appropriate function. Several negative regulators of Met signaling have been identified. Here we report that human Spry2 is induced by HGF/SF and negatively regulates HGF/SF-Met signaling. We show that overexpression of Spry2 inhibits cell proliferation, anchorage-independent cell growth, and migration in wound-healing and in vitro invasion assays. Measured in an electric cell-substrate impedance sensing biosensor, cell movement is restricted, because Spry2 dramatically facilitates cell attachment and spreading by enhancing focal adhesions and increasing stress fibers. An analysis of cell cycle distribution shows, unexpectedly, that Spry2-GFP cells are polyploid. Thus, as with FGF and EGF receptors, Spry2-GFP tempers downstream Met signaling in addition to its pronounced effect on cell adhesion, and it has properties suitable to be considered a tumor-suppressor protein.

引用

页码：5193 / 5202

页数：10

共 35 条

[21] Evidence that SPROUTY2 functions as an inhibitor of mouse embryonic lung growth and morphogenesis [J].