Rho GDP Dissociation Inhibitor 2 Suppresses Metastasis via Unconventional Regulation of RhoGTPases

被引：64

作者：

Moissoglu, Konstadinos ^{[1
]}

McRoberts, Kevin S. ^{[2
,3
]}

Meier, Jeremy A. ^{[1
]}

Theodorescu, Dan ^{[1
,2
,3
,7
]}

Schwartz, Martin A. ^{[1
,4
,5
,6
,7
]}

机构：

[1] Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22908 USA

[2] Univ Virginia, Dept Urol, Charlottesville, VA 22908 USA

[3] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA

[4] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA

[5] Univ Virginia, Dept Cell Biol, Charlottesville, VA 22908 USA

[6] Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22908 USA

[7] Univ Virginia, Mellon Urol Canc Res Inst, Charlottesville, VA 22908 USA

来源：

CANCER RESEARCH | 2009年 / 69卷 / 07期

关键词：

CELL MOTILITY; INVASION; BINDING; GENE; RAC; ACTIVATION; MIGRATION; RHOGD12; PROTEIN; INVOLVEMENT;

D O I：

10.1158/0008-5472.CAN-08-1397

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Rho GDP dissociation inhibitor 2 (RhoGDI2) has been identified as a metastasis suppressor in bladder and possibly other cancers. This protein is a member of a family of proteins that maintain Rho GTPases in the cytoplasm and inhibit their activation and function. To understand the mechanism of metastasis suppression, we compared effects of RhoGDI1 and RhoGDI2. Despite showing much stronger inhibition of metastasis, RhoGDI2 is a weak inhibitor of Rho GTPase membrane targeting and function. However, point mutants that increase or decrease the affinity of RhoGDI2 for GTPases abolished its ability to inhibit metastasis. Surprisingly, metastasis suppression correlates with increased rather than decreased Rac1 activity. These data show that RhoGDI2 metastasis inhibition works through Rho GTPases but via a mechanism distinct from inhibition of membrane association. [Cancer Res 2009;69(7):2838-44]

引用

页码：2838 / 2844

页数：7

共 29 条

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