title: Decreased eIF3e Expression Can Mediate Epithelial-to-Mesenchymal Transition through Activation of the TGFβ Signaling Pathway.
abstract: The eIF3e protein is a component of the multisubunit eIF3 complex, which is essential for cap-dependent translation initiation. Decreased eIF3e expression is often observed in breast and lung cancer and has been shown to induce epithelial-to-mesenchymal transition (EMT) in breast epithelial cells by an unknown mechanism. Here, we study the effect of decreased eIF3e expression in lung epithelial cells by creating stable clones of lung epithelial cells (A549) that express an eIF3e-targeting shRNA. Our data indicate that decreased eIF3e expression in lung epithelial cells leads to EMT, as it does in breast epithelial cells. Importantly, we show that decreased eIF3e expression in both lung and breast epithelial cells leads to the overproduction of the TGFβ cytokine and that inhibition of TGFβ signaling can reverse eIF3e-regulated EMT in lung epithelial cells. In addition, we discovered that several mRNAs that encode important EMT regulators are translated by a cap-independent mechanism when eIF3e levels are reduced. These findings indicate that EMT mediated by a decrease in eIF3e expression may be a general phenomenon in epithelial cells and that it requires activation and maintenance of the TGFβ signaling pathway.
  
  
  CONCLUSIONS
  These results indicate that inhibition of TGFβ signaling could be an efficient way to prevent metastasis in patients with NSCLC that display reduced eIF3e expression.
authors.affiliation: Atlantic Cancer Research Institute, Moncton, New Brunswick, Canada. Department of Biology, University of New Brunswick, Saint John, New Brunswick, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Desnoyers
authors.affiliation: Atlantic Cancer Research Institute, Moncton, New Brunswick, Canada.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Frost
authors.affiliation: Atlantic Cancer Research Institute, Moncton, New Brunswick, Canada.
authors.forename: Lynn
authors.initials: L
authors.lastname: Courteau
authors.affiliation: Atlantic Cancer Research Institute, Moncton, New Brunswick, Canada.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Wall
authors.affiliation: Atlantic Cancer Research Institute, Moncton, New Brunswick, Canada. Department of Biology, University of New Brunswick, Saint John, New Brunswick, Canada. Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada. Department of Chemistry and Biochemistry, Université de Moncton, Moncton, New Brunswick, Canada. stephenl@canceratl.ca.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Lewis
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition; D039621:Eukaryotic Initiation Factor-3 / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D039621:Eukaryotic Initiation Factor-3; D016212:Transforming Growth Factor beta