Abstract
Rho GTPase-activating proteins (RhoGAPs) are implicated in the development and progression of ovarian cancer. ARHGAP10 is a member of RhoGAP proteins and inactivates Cdc42 by converting GTP-bound form to GDP-bound form. Here, we aimed to evaluate ARHGAP10 expression profile and functions in ovarian cancer. The decreased expression of ARHGAP10 was found in 77.3% (58/75) of ovarian cancer tissues, compared with their non-tumorous counterparts. Furthermore, overall survival in ovarian cancer patients with higher expression of ARHGAP10 was longer than those with lower expression. Ectopic expression of ARHGAP10 in two ovarian cancer cell lines with lower expression of ARHGAP10 (A2780 and HO-8910) dramatically suppressed cell proliferation in vitro. In nude mice, its stable overexpression significantly inhibited the tumorigenicity of A2780 cells. We further demonstrated that overexpression of ARHGAP10 significantly inhibited cell adhesion, migration and invasion, resulted in cell arrest in G1 phase of cell cycle and a significant increase of apoptosis. Moreover, ARHGAP10 interacted with Cdc42 and overexpression of ARHGAP10 inhibited the activity of Cdc42 in A2780 cells. Gene set enrichment analysis on The Cancer Genome Atlas dataset showed that KEGG cell cycle, replication and base excision repair (BER) pathways were correlatively with the ARHGAP10 expression, which was further confirmed in ovarian cancer cells by western blotting. Hence, ARHGAP10 may serve as a tumor suppressor through inactivating Cdc42, as well as inhibiting cell cycle, replication and BER pathways. Our data suggest an important role of ARHGAP10 in the molecular etiology of cancer and implicate the potential application of ARHGAP10 in cancer therapy.
Highlights
GAP10 is an important member of Rho GTPase-activating proteins (RhoGAP),[2] which catalyze the conversion of active GTP-bound Rho GTPases to the inactive GDP-bound form, and suppress Rho GTPasesmediated cellular processes
Reduced expression of ARHGAP10 was correlated with poor prognosis of ovarian cancer
Kaplan–Meier analysis was performed to investigate the correlation of ARHGAP10 expression and prognosis
Summary
GAP10 ( known as ARHGAP21) is an important member of Rho GTPase-activating proteins (RhoGAP),[2] which catalyze the conversion of active GTP-bound Rho GTPases to the inactive GDP-bound form, and suppress Rho GTPasesmediated cellular processes. A series of recent studies has shown an association between ARHGAP10 and various cancers, such as head and neck squamous cell carcinoma,[14] gliomas[15] and prostate cancer.[4] Emerging evidence has liked other RhoGAPs to the development and progression of ovarian cancer.[16,17] Here, we aimed to evaluate ARHGAP10 expression and functions in ovarian cancer. Our study provides the evidences that ARHGAP10 expression is decreased in ovarian cancer, and it may be a prognosis factor and tumor suppressor for this disease
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