Ran GTPase protein promotes metastasis and invasion in pancreatic cancer by deregulating the expression of AR and CXCR4

被引：30

作者：

Deng, Lin ^{[1
,2
]}

Shang, Yulong ^{[1
]}

Guo, Shikong ^{[3
]}

Liu, Changhao ^{[1
]}

Zhou, Lin ^{[1
]}

Sun, Yi ^{[1
]}

Nie, Yongzhan ^{[1
]}

Fan, Daiming ^{[1
]}

Lu, Yuanyuan ^{[1
]}

Guo, Xuegang ^{[1
]}

机构：

[1] Fourth Mil Med Univ, Xijing Hosp Digest Dis, State Key Lab Canc Biol, Xian 710032, Shaanxi, Peoples R China

[2] Fourth Mil Med Univ, Tangdu Hosp, Dept Oncol, Xian 710032, Shaanxi, Peoples R China

[3] Fourth Mil Med Univ, Dept Orthoped Surg, Orthoped Oncol Inst Chinese PLA, Tangdu Hosp, Xian 710032, Shaanxi, Peoples R China

来源：

CANCER BIOLOGY & THERAPY | 2014年 / 15卷 / 08期

基金：

中国国家自然科学基金;

关键词：

Ran; pancreatic cancer; metastasis; invasion; PCR array; AR; CXCR4; ANDROGEN RECEPTOR; NUCLEAR TRANSPORT; PROSTATE-CANCER; CELL; PATHWAY; ACTIVATION; CARCINOMA;

D O I：

10.4161/cbt.29217

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Ran, a member of the RasGTPase family, has been showed to function in diverse cellular processes of cancer. In the present study, we examined the effects of Ran on the cell motility in pancreatic cancer cells and explored the possible mechanism of Ran's function in the metastasis of pancreatic cancer. We demonstrated that the expression of Ran was remarkably higher in lymph lode metastases than in primary pancreatic cancer tissues. In the functional studies, stable knockdown of Ran by shRNA could efficiently inhibit the migration and invasion of pancreatic cancer cells both in vitro and in vivo. By PCR array, we analyzed the differences in the expression levels of metastasis-associated genes before and after the downregulation of Ran, and it was showed that the regulation of pancreatic cancer metastasis by Ran was partially mediated by AR and CXCR4. We further confirmed that AR and CXCR4 were significantly decreased following knockdown of Ran. These data indicated that Ran could regulate the invasion and metastasis of pancreatic cancer cells through AR and CXCR4.

引用

页码：1087 / 1093

页数：7

共 27 条

[1] High expression of Ran GTPase is associated with local invasion and metastasis of human clear cell renal cell carcinoma [J].