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

被引:13
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
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
收藏
页码:2045 / 2056
页数:12
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