14-3-3σ attenuates RhoGDI2-induced cisplatin resistance through activation of Erk and p38 in gastric cancer cells
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In-Kyu Kim1,*, Sun-Mi Park1,*, Hee Jun Cho1,*, Kyoung Eun Baek1, In-Koo Nam1, Seung-Ho Park1, Ki-Jun Ryu1, Jinhyun Ryu2, Jungil Choi2, Soon-Chan Hong3, Jae Won Kim1, Chang Won Lee1, Sang Soo Kang2 and Jiyun Yoo1
1 Division of Applied Life Science/Research Institute of Life Science, Graduate School of Gyeongsang National University, Jinju, Korea.
2 Department of Anatomy and Neurobiology, Institute of Health Science, and Medical Research Center for Neural Dysfunction, School of Medicine, Gyeongsang National University, Jinju, Korea.
3 Department of Surgery, School of Medicine, Gyeongsang National University, Jinju, Korea.
* Contributed equally to this work.
Jiyun Yoo, email:
Sang Soo Kang, email:
Keywords: RhoGDI2, 14-3-3σ, gastric cancer, chemoresistance, metastasis
Received: August 27, 2013 Accepted: October 19, 2013 Published: October 19, 2013
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.
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