title: 14-3-3σ 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 14-3-3σ 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.
authors.affiliation: Division of Applied Life Science/Research Institute of Life Science, Graduate School of Gyeongsang National University, Jinju, Korea.
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Kim
authors.forename: Sun-Mi
authors.initials: SM
authors.lastname: Park
authors.forename: Hee Jun
authors.initials: HJ
authors.lastname: Cho
authors.forename: Kyoung Eun
authors.initials: KE
authors.lastname: Baek
authors.forename: In-Koo
authors.initials: IK
authors.lastname: Nam
authors.forename: Seung-Ho
authors.initials: SH
authors.lastname: Park
authors.forename: Ki-Jun
authors.initials: KJ
authors.lastname: Ryu
authors.forename: Jinhyun
authors.initials: J
authors.lastname: Ryu
authors.forename: Jungil
authors.initials: J
authors.lastname: Choi
authors.forename: Soon-Chan
authors.initials: SC
authors.lastname: Hong
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Chang Won
authors.initials: CW
authors.lastname: Lee
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Kang
authors.forename: Jiyun
authors.initials: J
authors.lastname: Yoo
mesh_terms: D048948:14-3-3 Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology*; D018450:Disease Progression; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D004789:Enzyme Activation; D005095:Exoribonucleases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D061986:MCF-7 Cells; D009362:Neoplasm Metastasis; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; C569658:ARHGDIB protein, human; D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005095:Exoribonucleases; C413442:SFN protein, human; D002945:Cisplatin