YAP Regulates Actin Dynamics through ARHGAP29 and Promotes Metastasis Qiao, Yiting et al. Cell Reports, Volume 19, Issue 8, 1495 - 1502
Abstract:
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.
License type:
http://creativecommons.org/licenses/by-nc-nd/4.0/
Funding Info:
We thank Professors Michael Sheetz and Alexander Bershadsky for their expert advice and support of our research project. This work was supported by seed grants from the National University of Singapore ( R-185-000-2710-133 & 733 ), the Mechanobiology Institute ( R-714-018-006-271 ), and the Institute of Molecular and Cell Biology ( M-R02010 ) to M.S. All recombinant cDNA constructs reported here have been deposited to ADDGENE.
Description:
This is a version of record published in Cell Reports. The final authenticated version is available online at: https://doi.org/10.1016/j.celrep.2017.04.075