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

• DOI: 10.18632/oncotarget.1334
• Publication Date: 2015-09-16T21:45:41Z
• Authors: In-Kyu Kim; Sun-Mi Park; Hee Jun Cho; Kyoung Eun Baek; In-Koo Nam; Seung-Ho Park; Ki-Jun Ryu; Jinhyun Ryu; Jungil Choi; Soon-Chan Hong; Jae Won Kim; Chang Won Lee; Sang Soo Kang; Jiyun Yoo
• Keywords: MAP Kinase Signaling System; Down-Regulation; Apoptosis; Transfection; 3. Good health; Enzyme Activation; 03 medical and health sciences; 0302 clinical medicine; 14-3-3 Proteins; Cell Movement; Drug Resistance, Neoplasm; Stomach Neoplasms; Cell Line, Tumor; Exoribonucleases; Biomarkers, Tumor; Disease Progression; MCF-7 Cells; Humans; Cisplatin; Neoplasm Metastasis; RNA, Small Interfering; Extracellular Signal-Regulated MAP Kinases; HeLa Cells

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