SMURF1-mediated ubiquitination of ARHGAP26 promotes ovarian cancer cell invasion and migration.

Authors:
Shaoyun Chen
Shaoyun Chen
Toho University School of Medicine
Japan
Yao Li
Yao Li
College of Life Science
China
Yanling Gao
Yanling Gao
Zunyi Medical College
China
Shuying Huang
Shuying Huang
Jiangxi University of Finance and Economics
China
Hongping Li
Hongping Li
Center for Molecular Sciences
Yuanfang Zhu
Yuanfang Zhu
BGI-Shenzhen

Exp Mol Med 2019 Apr 19;51(4):46. Epub 2019 Apr 19.

Department of Obstetrics and Gynecology, Bao'an Maternity and Child Health Hospital, Jinan University, Shenzhen, 518100, China.

Rho GTPase-activating protein 26 (ARHGAP26) is a negative regulator of the Rho family that converts the small GTP-binding protein RhoA (GTP-RhoA) to its inactive GDP-bound form and is a putative tumor suppressor gene associated with cell growth and migration. Here, the involvement of ARHGAP26 in ovarian cancer cell proliferation and migration was investigated. In this study, low ARHGAP26 expression was observed in ovarian cancer tissues and was associated with a poor overall survival and higher β-catenin expression in patients with ovarian cancer. A2780 and HEY cells with ARHGAP26 upregulation showed decreased cell proliferation, migration, and invasion, along with decreased GTP-RhoA, β-catenin, VEGF, MMP2, and MMP7 expression. ARHGAP26 upregulation in A2780 cells also inhibited lung metastasis in vivo. SKOV3 cells with ARHGAP26 downregulation demonstrated an inverse effect, which was inhibited by ARHGAP26 overexpression or DKK1, an antagonist of the β-catenin pathway. SMURF1, an E3 ubiquitin ligase, interacted with and induced ubiquitination of ARHGAP26. ARHGAP26 upregulation in SKOV3 cells significantly inhibited SMURF1 upregulation-induced cell migration and invasion. Overall, SMURF1-mediated ubiquitination of ARHGAP26 may promote invasion and migration of ovarian cancer cells via the β-catenin pathway.

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http://www.nature.com/articles/s12276-019-0236-0
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http://dx.doi.org/10.1038/s12276-019-0236-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474862PMC
April 2019
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