title: ARHGAP10, downregulated in ovarian cancer, suppresses tumorigenicity of ovarian cancer cells.
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.
authors.affiliation: Department of Gynecology & Obstetrics, Yangpu Hospital, School of Medicine, Tongji University, Shanghai 200090, China.|Institute of Gynecological Minimally Invasive Medicine, School of Medicine, Tongji University, Shanghai 200090, China.
authors.forename: N
authors.initials: N
authors.lastname: Luo
authors.affiliation: Department of Gynecology & Obstetrics, Yangpu Hospital, School of Medicine, Tongji University, Shanghai 200090, China.|Institute of Gynecological Minimally Invasive Medicine, School of Medicine, Tongji University, Shanghai 200090, China.
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Gynecology & Obstetrics, Yangpu Hospital, School of Medicine, Tongji University, Shanghai 200090, China.|Institute of Gynecological Minimally Invasive Medicine, School of Medicine, Tongji University, Shanghai 200090, China.
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Gynecology & Obstetrics, Yangpu Hospital, School of Medicine, Tongji University, Shanghai 200090, China.|Institute of Gynecological Minimally Invasive Medicine, School of Medicine, Tongji University, Shanghai 200090, China.
authors.forename: W
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Gynecology & Obstetrics, Yangpu Hospital, School of Medicine, Tongji University, Shanghai 200090, China.|Institute of Gynecological Minimally Invasive Medicine, School of Medicine, Tongji University, Shanghai 200090, China.
authors.forename: X
authors.initials: X
authors.lastname: Qu
authors.affiliation: Department of Gynecology & Obstetrics, Yangpu Hospital, School of Medicine, Tongji University, Shanghai 200090, China.|Institute of Gynecological Minimally Invasive Medicine, School of Medicine, Tongji University, Shanghai 200090, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Cheng
mesh_terms: D000818:Animals; D015536:Down-Regulation; D005260:Female; D020690:GTPase-Activating Proteins / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C486050:ARHGAP10 protein, human; C425467:Arhgap10 protein, mouse; C581598:Cdc42 protein, mouse; D020690:GTPase-Activating Proteins; D025521:Tumor Suppressor Proteins; D020764:cdc42 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein