title: PLCγ is required for RhoGDI2-mediated cisplatin resistance in gastric cancer.
abstract: Rho GDP dissociation inhibitor 2 (RhoGDI2) is a regulator of the Rho family GTPases. Recent work from our laboratory suggests that RhoGDI2 expression potentially enhances resistance to cisplatin as well as promotes tumor growth and malignant progression in gastric cancer. In this study, we demonstrate that phospholipase C-gamma (PLCγ) is required for RhoGDI2-mediated cisplatin resistance and cancer cell invasion in gastric cancer. The levels of phosphorylated PLCγ are markedly enhanced in RhoGDI2-overexpressing SNU-484 cells and, by contrast, repressed in RhoGDI2-depleted MKN-28 cells. Depletion of PLCγ expression or inhibition of its activity not only significantly increases cisplatin-induced apoptosis but also suppresses the invasive ability of RhoGDI2-overexpressing SNU-484 cells. Taken together, our results suggest that PLCγ plays a key role in RhoGDI2-mediated cisplatin resistance and cell invasion in gastric cancer cells.
authors: Department of Microbiology/Research Institute of Life Science, College of Natural Sciences, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors: Hee Jun
authors: HJ
authors: Cho
authors: Kyoung Eun
authors: KE
authors: Baek
authors: In-Koo
authors: IK
authors: Nam
authors: Sun-Mi
authors: SM
authors: Park
authors: In-Kyu
authors: IK
authors: Kim
authors: Seung-Ho
authors: SH
authors: Park
authors: Min-Ju
authors: MJ
authors: Im
authors: Ki-Jun
authors: KJ
authors: Ryu
authors: Jong-Min
authors: JM
authors: Yoo
authors: Soon-Chan
authors: SC
authors: Hong
authors: Jae Won
authors: JW
authors: Kim
authors: Chang Won
authors: CW
authors: Lee
authors: Jiyun
authors: J
authors: Yoo
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004789:Enzyme Activation; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness; D051966:Phospholipase C gamma / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
chemical_list: C569658:ARHGDIB protein, human; D000970:Antineoplastic Agents; D020730:Guanine Nucleotide Dissociation Inhibitors; D025521:Tumor Suppressor Proteins; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D051966:Phospholipase C gamma; D002945:Cisplatin