A novel function for Cyclin A2: Control of cell invasion via RhoA signaling

被引：106

作者：

Arsic, Nikola ^{[1
,3
,4
]}

Bendris, Nawal ^{[1
,3
,4
]}

Peter, Marion ^{[1
,3
,4
]}

Begon-Pescia, Christina ^{[1
,3
,4
]}

Rebouissou, Cosette ^{[1
,3
,4
]}

Gadea, Gilles ^{[2
]}

Bouquier, Nathalie ^{[2
]}

Bibeau, Frederic ^{[5
]}

Lemmers, Benedicte ^{[1
,3
,4
]}

Blanchard, Jean Marie ^{[1
,3
,4
]}

机构：

[1] CNRS, Inst Genet Mol Montpellier, F-34293 Montpellier, France

[2] CNRS, Ctr Rech Biochim Macromol, F-34293 Montpellier, France

[3] Univ Montpellier 2, F-34095 Montpellier, France

[4] Univ Montpellier 1, F-34967 Montpellier, France

[5] Ctr Reg Lutte Canc Val dAurelle Paul Lamarque, F-34298 Montpellier, France

来源：

JOURNAL OF CELL BIOLOGY | 2012年 / 196卷 / 01期

关键词：

NUCLEOTIDE EXCHANGE FACTOR; KINASE-ACTIVITY; PROTEIN-KINASE; EXPRESSION; MIGRATION; RAC; CANCER; P27(KIP1); GTPASES; CARCINOMA;

D O I：

10.1083/jcb.201102085

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Cyclin A2 plays a key role in cell cycle regulation. It is essential in embryonic cells and in the hematopoietic lineage yet dispensable in fibroblasts. In this paper, we demonstrate that Cyclin A2-depleted cells display a cortical distribution of actin filaments and increased migration. These defects are rescued by restoration of wild-type Cyclin A2, which directly interacts with RhoA, or by a Cyclin A2 mutant unable to associate with Cdk. In vitro, Cyclin A2 potentiates the exchange activity of a RhoA-specific guanine nucleotide exchange factor. Consistent with this, Cyclin A2 depletion enhances migration of fibroblasts and invasiveness of transformed cells via down-regulation of RhoA activity. Moreover, Cyclin A2 expression is lower in metastases relative to primary colon adenocarcinoma in matched human tumors. All together, these data show that Cyclin A2 negatively controls cell motility by promoting RhoA activation, thus demonstrating a novel Cyclin A2 function in cytoskeletal rearrangements and cell migration.

引用

页码：147 / 162

页数：16

共 61 条

[1] Expression of cyclins A and D and p21(waf1/cip1) proteins in renal cell cancer and their relation to clinicopathological variables and patient survival [J].