title: TGF-β1 regulates cell fate during epithelial-mesenchymal transition by upregulating survivin.
abstract: Members of the transforming growth factor beta (TGF-β) superfamily are multifunctional cytokines that regulate several cellular processes, including cell cycle arrest, differentiation, morphogenesis, and apoptosis. TGF-β promotes extracellular matrix production and morphological change. Morphogenetic responses to TGF-β include cell migration and epithelial-mesenchymal transition (EMT), which are critical during embryogenesis, development of fibrotic diseases, and the spreading of advanced carcinomas. The purpose of this study was to clarify how TGF-β regulates the fate of retinal pigment epithelial (RPE) cells. TGF-β1 promoted cell cycle progression and phosphorylation of retinoblastoma protein (Rb) in ARPE-19 cells. TGF-β1 induced survivin expression, which in turn stabilized tubulin and Aurora B. RT-PCR and western blot analysis revealed that survivin expression increased in ARPE-19 cells following TGF-β1 treatment. When survivin was depleted, TGF-β1 induced cell cycle arrest and apoptosis and also reduced Rb phosphorylation. In conclusion, the present study shows that induction of EMT in human RPE cells upregulates survivin, leading to survivin-dependent inhibition of cell cycle arrest and apoptosis. Whether cells undergo EMT or apoptosis in response to TGF-β1 is dependent on their cell cycle state, and TGF-β1 regulates the cell cycle via survivin.
authors.affiliation: Catholic Institutes for Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Korea. leeje2937@gmail.com
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: J-H
authors.initials: JH
authors.lastname: Choi
authors.forename: C-K
authors.initials: CK
authors.lastname: Joo
mesh_terms: D017209:Apoptosis; D064107:Aurora Kinase B / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism; D008938:Mitosis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D055550:Protein Stability; D055213:Retinal Pigment Epithelium / Q000502:physiology; D000077022:Survivin; D015533:Transcriptional Activation; D053773:Transforming Growth Factor beta1 / Q000502:physiology*; D014404:Tubulin / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D014404:Tubulin; D019869:Phosphatidylinositol 3-Kinases; C576921:AURKB protein, human; D064107:Aurora Kinase B