title: The C3G/Rap1 pathway promotes secretion of MMP-2 and MMP-9 and is involved in serous ovarian cancer metastasis.
abstract: Complete resection is pivotal to improve survival to epithelial ovarian cancer (EOC). Crk SH3-domain-binding guanine nucleotide-releasing factor (C3G) is involved in multiple signaling pathways and it has opposite roles in different cancers. The present study aimed to identify C3G expression in ovarian tissue samples from patients with EOC and to explore its association with tumor grade. Eighty-seven archival paraffin-embedded, formalin-fixed, ovarian cancer tissues with serous histology were stained for C3G by immunohistochemistry. To evaluate the contribution of C3G to Rap1 activity, 36 patients with serous ovarian cancer (SOC) were investigated. Additionally, C3G was knocked down in SKOV3 and HEY cells. C3G regulated Rap1 activity and high Rap1 activity was correlated with poor differentiation, advanced FIGO stage, and unsuccessful cytoreductive surgery of SOC. Knockdown of C3G suppressed cell invasion, intravasation and extravasation, and reduced Rap1 activity and secretion of matrix metalloproteinase (MMP)-2 and MMP-9. C3G-mediated activation of Rap1 could direct the tumor pattern of human SOC by promoting the secretion of MMP-2 and MMP-9. These results suggest that C3G is involved in the metastatic spread of EOC.
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Department of Obstetrics & Gynecology, Central Hospital of Xi'an, Xi'an 710003, China.
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Che
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Department of Obstetrics & Gynecology, Maternal and Child Care Service Centre of Chongqing, Chongqing 400016, China.
authors.forename: Shu-Juan
authors.initials: SJ
authors.lastname: Luo
authors.affiliation: Department of Geriatrics, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Min
authors.initials: M
authors.lastname: Cheng
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yi-Meng
authors.initials: YM
authors.lastname: Gao
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jie-Min
authors.initials: JM
authors.lastname: Dai
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Huan
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Peng
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Wen-Yan
authors.initials: WY
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pathology, Basic Medical School of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: linghu_hua@yahoo.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Linghu
mesh_terms: D000818:Animals; D018572:Disease-Free Survival; D005260:Female; D020735:Guanine Nucleotide-Releasing Factor 2 / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000201:enzymology* / Q000401:mortality / Q000556:secondary; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000556:secondary; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins / Q000378:metabolism*
chemical_list: D020735:Guanine Nucleotide-Releasing Factor 2; D000089804:Shelterin Complex; C440809:TERF2IP protein, human; D034501:Telomere-Binding Proteins; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: C3G; Metastasis; Rap1 activity; Serous ovarian cancer