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

ABSTRACT: 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? expression, which suggests that 14-3-3? is a target of gastric cancer metastasis and the chemoresistance-promoting effect of RhoGDI2. Herein, we evaluated whether 14-3-3? 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? mRNA and protein expression. Depletion of 14-3-3? in SNU-484 control cells enhanced cisplatin resistance, whereas restoration of 14-3-3? 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? expression, and that decreased activities of these kinases were critical for RhoGDI2-induced cisplatin resistance. In conclusion, 14-3-3? is a RhoGDI2-regulated gene that appears to be important for suppressing the chemoresistance of gastric cancer cells.

SUBMITTER: Kim IK 

PROVIDER: S-EPMC3875768 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature