YAP Regulates Actin Dynamics through ARHGAP29 and Promotes Metastasis

• DOI: 10.1016/j.celrep.2017.04.075
• Publication Date: 2017-05-23T18:08:22Z
• Authors: Yiting Qiao; Jianxiang Chen; Ying Bena Lim; Megan Louise Finc...; Veerabrahma Prata...; Lei Qin; Tingting Jiang; Boon Chuan Low; Himanshu Singh; Chwee Teck Lim; Marius Sudol
• Keywords: rho GTP-Binding Proteins; 0301 basic medicine; Transcription, Genetic; QH301-705.5; Mice; 03 medical and health sciences; Stomach Neoplasms; Cell Line, Tumor; metastasis; Animals; Humans; Biology (General); Neoplasm Metastasis; Adaptor Proteins, Signal Transducing; atomic force microscopy; gastric cancer; GTPase-Activating Proteins; Lim Kinases; RhoA; YAP-Signaling Proteins; Phosphoproteins; Actins; ARHGAP29; 3. Good health; Actin Depolymerizing Factors; YAP; actin; Signal Transduction; Transcription Factors

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.