14-3-3σ attenuates RhoGDI2-induced cisplatin resistance through activation of Erk and p38 in gastric cancer cells

被引：14

作者：

Kim, In-Kyu ^{[1
]}

Park, Sun-Mi ^{[1
]}

Cho, Hee Jun ^{[1
]}

Baek, Kyoung Eun ^{[1
]}

Nam, In-Koo ^{[1
]}

Park, Seung-Ho ^{[1
]}

Ryu, Ki-Jun ^{[1
]}

Ryu, Jinhyun ^{[2
,3
]}

Choi, Jungil ^{[2
,3
]}

Hong, Soon-Chan ^{[4
]}

Kim, Jae Won ^{[1
]}

Lee, Chang Won ^{[1
]}

Kang, Sang Soo ^{[2
,3
]}

Yoo, Jiyun ^{[1
]}

机构：

[1] Gyeongsang Natl Univ, Grad Sch, Life Sci Res Inst, Div Appl Life Sci, Jinju, South Korea

[2] Gyeongsang Natl Univ, Sch Med, Dept Anat & Neurobiol, Inst Hlth Sci, Jinju, South Korea

[3] Gyeongsang Natl Univ, Sch Med, Med Res Ctr Neural Dysfunct, Jinju, South Korea

[4] Gyeongsang Natl Univ, Sch Med, Dept Surg, Jinju, South Korea

来源：

ONCOTARGET | 2013年 / 4卷 / 11期

基金：

新加坡国家研究基金会;

关键词：

RhoGDI2; 14-3-3; sigma; gastric cancer; chemoresistance; metastasis; RHO GTPASES; RHOGDI2; CHEMOTHERAPY; METASTASIS; EXPRESSION; 5-FLUOROURACIL; PROTEINS; D4-GDI; ALPHA; PROGRESSION;

D O I：

10.18632/oncotarget.1334

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Rho GDP dissociation inhibitor 2 (RhoGDI2) promotes tumor growth and malignant progression and enhances chemoresistance of gastric cancer. Recently, we noted an inverse correlation between RhoGDI2 and 14-3-3 sigma expression, which suggests that 14-3-3 sigma is a target of gastric cancer metastasis and the chemoresistance-promoting effect of RhoGDI2. Herein, we evaluated whether 14-3-3 sigma is regulated by RhoGDI2 and is functionally important for the RhoGDI2-induced cisplatin resistance of gastric cancer cells. We used highly metastatic and cisplatin-resistant RhoGDI2-overexpressing SNU-484 cells and observed decreased 14-3-3 sigma mRNA and protein expression. Depletion of 14-3-3 sigma in SNU-484 control cells enhanced cisplatin resistance, whereas restoration of 14-3-3 sigma in RhoGDI2-overexpressing SNU-484 cells impaired cisplatin resistance in vitro and in vivo. We also found that the phosphorylation levels of Erk and p38 kinases significantly decreased in RhoGDI2-overexpressing SNU-484 cells and recovered after 14-3-3 sigma expression, and that decreased activities of these kinases were critical for RhoGDI2-induced cisplatin resistance. In conclusion, 14-3-3 sigma is a RhoGDI2-regulated gene that appears to be important for suppressing the chemoresistance of gastric cancer cells.

引用

页码：2045 / 2056

页数：12

共 46 条

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