YAP Regulates Actin Dynamics through ARHGAP29 and Promotes Metastasis
Yiting Qiao1, Jianxiang Chen2, Ying Bena Lim3
1Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, MD9, 2 Medical Drive, Singapore 117593, Singapore.
Cell Reports
|May 25, 2017
Summary
Yes-associated protein (YAP) promotes gastric cancer metastasis by increasing ARHGAP29, which destabilizes the actin cytoskeleton. This YAP-ARHGAP29 pathway enhances cell migration and is linked to poorer patient survival.
Area of Science:
- Cell Biology
- Molecular Oncology
- Biochemistry
Background:
- The Hippo pathway, particularly Yes-associated protein (YAP), is mechanistically regulated and influences the cytoskeleton.
- YAP has been implicated in regulating the actomyosin network by suppressing Rho GTPase.
Purpose of the Study:
- To identify YAP transcriptional targets involved in cytoskeletal regulation in gastric cancer.
- To elucidate the role of YAP-mediated ARHGAP29 expression in gastric cancer cell migration and metastasis.
Main Methods:
- Utilized a human gastric cancer cell line to identify YAP transcriptional targets.
- Investigated the effect of YAP on ARHGAP29 expression and the RhoA-LIMK-cofilin pathway.
- Analyzed ARHGAP29 expression in circulating tumor cells (CTCs) and primary tumors in a mouse model.
- Correlated ARHGAP29 expression with patient survival data.
Main Results:
- Identified ARHGAP29 as a YAP transcriptional target in human gastric cancer cells.
- YAP overexpression upregulates ARHGAP29, suppressing the RhoA-LIMK-cofilin pathway and destabilizing F-actin.
- Increased ARHGAP29 RNA levels were observed in CTCs compared to primary tumor cells, correlating with metastatic potential.
- Higher ARHGAP29 expression in human gastric cancer patients correlated with reduced survival.
Conclusions:
- YAP promotes gastric cancer cell migration and metastasis through the upregulation of ARHGAP29, impacting actin dynamics.
- The YAP-ARHGAP29 axis represents a novel mechanism contributing to cancer progression and offers potential therapeutic targets.
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