Che Ya-Ling, Luo Shu-Juan, Li Gang, Cheng Min, Gao Yi-Meng, Li Xue-Mei, Dai Jie-Min, He Huan, Wang Jin, Peng Hui-Juan, Zhang Yu, Li Wen-Yan, Wang Hui, Liu Bin, Linghu Hua
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.
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.
Cancer Lett. 2015 Apr 10;359(2):241-9. doi: 10.1016/j.canlet.2015.01.019. Epub 2015 Jan 21.
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.
完整切除对于提高上皮性卵巢癌（EOC）患者的生存率至关重要。Crk SH3结构域结合鸟嘌呤核苷酸释放因子（C3G）参与多种信号通路，并且在不同癌症中具有相反的作用。本研究旨在确定EOC患者卵巢组织样本中C3G的表达情况，并探讨其与肿瘤分级的关系。采用免疫组织化学方法对87例福尔马林固定、石蜡包埋的浆液性组织学类型的卵巢癌组织进行C3G染色。为了评估C3G对Rap1活性的作用，对36例浆液性卵巢癌（SOC）患者进行了研究。此外，在SKOV3和HEY细胞中敲低C3G。C3G调节Rap1活性，高Rap1活性与SOC的低分化、国际妇产科联盟（FIGO）分期晚期及细胞减灭术失败相关。敲低C3G可抑制细胞侵袭、内渗和外渗，并降低Rap1活性以及基质金属蛋白酶（MMP）-2和MMP-9的分泌。C3G介导Rap1的激活可通过促进MMP-2和MMP-9的分泌来指导人类SOC的肿瘤模式。这些结果表明C3G参与了EOC的转移扩散。
