The C3G/Rap1 pathway promotes secretion of MMP-2 and MMP-9 and is involved in serous ovarian cancer metastasis

被引：100

作者：

Che, Ya-Ling ^{[1
,4
]}

Luo, Shu-Juan ^{[1
,5
]}

Li, Gang ^{[2
]}

Cheng, Min ^{[1
]}

Gao, Yi-Meng ^{[1
]}

Li, Xue-Mei ^{[1
]}

Dai, Jie-Min ^{[1
]}

He, Huan ^{[1
]}

Wang, Jin ^{[1
]}

Peng, Hui-Juan ^{[1
]}

Zhang, Yu ^{[1
]}

Li, Wen-Yan ^{[1
]}

Wang, Hui ^{[1
]}

Liu, Bin ^{[3
]}

Hua Linghu ^{[1
]}

机构：

[1] Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, Chongqing 400016, Peoples R China

[2] Chongqing Med Univ, Affiliated Hosp 1, Dept Geriatr, Chongqing 400016, Peoples R China

[3] Chongqing Med Univ, Basic Med Sch, Dept Pathol, Chongqing 400016, Peoples R China

[4] Cent Hosp, Dept Obstet & Gynecol, Xian 710003, Peoples R China

[5] Ctr Chongqing, Dept Obstet & Gynecol, Maternal & Child Care Serv, Chongqing 400016, Peoples R China

来源：

CANCER LETTERS | 2015年 / 359卷 / 02期

基金：

中国国家自然科学基金;

关键词：

C3G; Rap1; activity; Metastasis; Serous ovarian cancer; NUCLEOTIDE-EXCHANGE FACTOR; FACTOR C3G; RHO GTPASES; PROTEIN; DOMAIN; CELLS; ACTIVATION; SURVIVAL; RAP1; CYTOREDUCTION;

D O I：

10.1016/j.canlet.2015.01.019

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

引用

页码：241 / 249

页数：9

共 39 条

[1]

CrkL activates integrin-mediated hematopoietic cell adhesion through the guanine nucleotide exchange factor C3G [J].