YAP Regulates Actin Dynamics through ARHGAP29 and Promotes Metastasis

被引：209

作者：

Qiao, Yiting ^{[1
]}

Chen, Jianxiang ^{[2
,3
]}

Lim, Ying Bena ^{[4
,5
]}

Finch-Edmondson, Megan Louise ^{[6
]}

Seshachalam, Veerabrahma Pratap ^{[2
]}

Qin, Lei ^{[6
]}

Jiang, Tingting ^{[7
]}

Low, Boon Chuan ^{[6
,7
]}

Singh, Himanshu ^{[4
,5
]}

Lim, Chwee Teck ^{[4
,5
,6
]}

Sudol, Marius ^{[1
,3
,6
]}

机构：

[1] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, MD9,2 Med Dr, Singapore 117593, Singapore

[2] Natl Canc Ctr Singapore, 11 Hosp Dr, Singapore 169610, Singapore

[3] Agcy Sci Technol & Res, IMCB, 61 Biopolis Dr, Singapore 138673, Singapore

[4] Natl Univ Singapore, Dept Biomed Engn, 4 Engn Dr 3, Singapore 117583, Singapore

[5] SMART Infect Dis IRG, 1 CREATE Way,10-01 CREATE Tower, Singapore 138602, Singapore

[6] Natl Univ Singapore, Mechanobiol Inst, 5A Engn Dr 1, Singapore 117411, Singapore

[7] Natl Univ Singapore, Dept Biol Sci, 16 Sci Dr 4, Singapore 117558, Singapore

来源：

CELL REPORTS | 2017年 / 19卷 / 08期

关键词：

CIRCULATING TUMOR-CELLS; HIPPO SIGNALING PATHWAY; YES-ASSOCIATED PROTEIN; GASTRIC-CANCER; RHO-GTPASES; LIM-KINASE; CYTOSKELETON; ORGANIZATION; MIGRATION; YAP/TAZ;

D O I：

10.1016/j.celrep.2017.04.075

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Yes-associated protein (YAP) is regulated by mechanical cues via the interaction of the Hippo pathway with cytoskeleton. Previous studies showed that YAP plays a role in regulating the actomyosin network by suppressing Rho GTPase in medaka fish. Here, we identify Rho GTPase activating protein 29 (ARHGAP29) as a transcriptional target of YAP in a human gastric cancer cell line. YAP promotes the expression of ARHGAP29 to suppress the RhoA-LIMK-cofilin pathway, destabilizing F-actin. The overexpression of YAP causes cytoskeletal rearrangement by altering the dynamics of F-actin/G-actin turnover, thus promoting migration. In a mouse model, circulating tumor cells (CTCs) exhibit an increased ARHGAP29 RNA level compared with cells at primary tumor sites, and the metastatic potential of CTCs is positively correlated with ARHGAP29 expression. Moreover, increased ARHGAP29 expression is correlated with shortened survival of human gastric cancer patients. Our study provides a model to understand YAP's contribution to cancer metastasis via regulation of actin dynamics.

引用

页码：1495 / 1502

页数：8

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