title: Proteomics-based strategy to delineate the molecular mechanisms of RhoGDI2-induced metastasis and drug resistance in gastric cancer.
abstract: Rho GDP dissociation inhibitor 2 (RhoGDI2) was initially identified as a regulator of the Rho family of GTPases. Our recent works suggest that RhoGDI2 promotes tumor growth and malignant progression, as well as enhances chemoresistance in gastric cancer. Here, we delineate the mechanism by which RhoGDI2 promotes gastric cancer cell invasion and chemoresistance using two-dimensional gel electrophoresis (2-DE) on proteins derived from a RhoGDI2-overexpressing SNU-484 human gastric cancer cell line and control cells. Differentially expressed proteins were identified using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF-MS). In total, 47 differential protein spots were identified; 33 were upregulated, and 14 were downregulated by RhoGDI2 overexpression. Upregulation of SAE1, Cathepsin D, Cofilin1, CIAPIN1, and PAK2 proteins was validated by Western blot analysis. Loss-of-function analysis using small interference RNA (siRNA) directed against candidate genes reveals the need for CIAPIN1 and PAK2 in RhoGDI2-induced cancer cell invasion and Cathepsin D and PAK2 in RhoGDI2-mediated chemoresistance in gastric cancer cells. These data extend our understanding of the genes that act downstream of RhoGDI2 during the progression of gastric cancer and the acquisition of chemoresistance.
authors.affiliation: Department of Microbiology/Research Institute of Life Science, College of Natural Sciences, Gyeongsang National University, Jinju, Korea.
authors.forename: Hee Jun
authors.initials: HJ
authors.lastname: Cho
authors.forename: Kyoung Eun
authors.initials: KE
authors.lastname: Baek
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Kim
authors.forename: Sun-Mi
authors.initials: SM
authors.lastname: Park
authors.forename: Yeong-Lim
authors.initials: YL
authors.lastname: Choi
authors.forename: In-Koo
authors.initials: IK
authors.lastname: Nam
authors.forename: Seung-Ho
authors.initials: SH
authors.lastname: Park
authors.forename: Min-Ju
authors.initials: MJ
authors.lastname: Im
authors.forename: Jong-Min
authors.initials: JM
authors.lastname: Yoo
authors.forename: Ki-Jun
authors.initials: KJ
authors.lastname: Ryu
authors.forename: Young Taek
authors.initials: YT
authors.lastname: Oh
authors.forename: Soon-Chan
authors.initials: SC
authors.lastname: Hong
authors.forename: Oh-Hyung
authors.initials: OH
authors.lastname: Kwon
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Chang Won
authors.initials: CW
authors.lastname: Lee
authors.forename: Jiyun
authors.initials: J
authors.lastname: Yoo
mesh_terms: D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D015180:Electrophoresis, Gel, Two-Dimensional; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000378:metabolism; D009362:Neoplasm Metastasis; D020543:Proteome / Q000032:analysis / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation; D054462:p21-Activated Kinases / Q000032:analysis / Q000378:metabolism; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
chemical_list: C569658:ARHGDIB protein, human; C489114:CIAPIN1 protein, human; D020730:Guanine Nucleotide Dissociation Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D020543:Proteome; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; C515907:PAK2 protein, human; D054462:p21-Activated Kinases