title: Mechanisms of RhoGDI2 mediated lung cancer epithelial-mesenchymal transition suppression.
abstract: BACKGROUND
  The aim of this study was to evaluate the function of RhoGDI2 in lung cancer epithelial-mesenchymal transition (EMT) process and to illustrate the underlying mechanisms that will lead to improvement of lung cancer treatment.
  
  
  METHODS
  The RhoGDI2 knock-down and overexpressing A549 cell lines were first constructed. The influence of RhoGDI2 on cytoskeleton in A549 cells was studied using two approaches: G-LISA-based Rac1 activity measurement and immunostaining-based F-actin distribution. The expression levels of key EMT genes were analyzed using real time quantitative polymerase chain reaction (RT-qPCR), western blot and immunostaining in untreated and RhoGDI2 knock-down or overexpressing A549 cells in both in vivo and in vitro experimental settings.
  
  
  RESULTS
  Our study showed that the activity of Rac1, a key gene that is crucial for the initiation and metastasis of human lung adenocarcinoma, causing the redistribution of F-actin with partial loss of cell-cell adhesions and stress fibers, was significantly suppressed by RhoGDI2. RhoGDI2 promoted the expression of EMT marker gene E-cadherin and repressed EMT promoting genes Slug, Snail, α-SMA in both A549 cells and lung and liver organs derived from the mouse models. Knocking-down RhoGDI2 induced abnormal morphology for lung organs.
  
  
  CONCLUSIONS
  These findings indicate that RhoGDI2 repressed the activity of Rac1 and may be involved in the rearrangement of cytoskeleton in lung cancer cells. RhoGDI2 suppresses the metastasis of lung cancer mediated through EMT by regulating the expression of key genes such as E-cadherin, Slug, Snail and α-SMA in both in vivo and in vitro models.
authors.affiliation: Department of Geriatrics, Shengjing Hospital, China Medical University, Shenyang, China.
authors.forename: Huiyan
authors.initials: H
authors.lastname: Niu
authors.forename: Baogang
authors.initials: B
authors.lastname: Wu
authors.forename: Hongfang
authors.initials: H
authors.lastname: Jiang
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Peng
authors.forename: Ping
authors.initials: P
authors.lastname: He
mesh_terms: D000199:Actins / Q000235:genetics; D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D020830:rac1 GTP-Binding Protein / Q000096:biosynthesis / Q000235:genetics*; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000199:Actins; C107953:RAC1 protein, human; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D020830:rac1 GTP-Binding Protein