title: Ran GTPase induces EMT and enhances invasion in non-small cell lung cancer cells through activation of PI3K-AKT pathway.
abstract: Ras-related nuclear protein (Ran) GTPase is upregulated in non-small cell lung cancer (NSCLC) cells and is required for NSCLC cell survival. However, the effect of Ran on NSCLC cell invasion and epithelial to mesenchymal transition (EMT) remains unclear. This study found that Ran expression was much higher in highly invasive NSCLC cells than in lowly invasive NSCLC cells. Ectopic expression of Ran enhanced invasion and induced EMT in NSCLC cells. Inhibition of the PI3K-AKT pathway by LY294002, but not the MEK-ERK pathway by PD98509, reversed the above effects in these cells induced by Ran overexpression. In conclusion, our findings demonstrate that Ran induces EMT and enhances invasion in NSCLC cells through the activation of PI3K-AKT signaling. Thus, Ran may be a potential target for NSCLC therapeutic intervention.
authors.affiliation: Department of Thoracic Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, PR China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Ning
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Yaoguo
authors.initials: Y
authors.lastname: Lang
authors.forename: Shidong
authors.initials: S
authors.lastname: Xu
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000473:pathology*; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology*; D020935:MAP Kinase Signaling System; D009025:Morpholines / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction; D020931:ran GTP-Binding Protein / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; C120587:RAN protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D020931:ran GTP-Binding Protein