title: TGF-β signaling and epithelial-mesenchymal transition in cancer progression.
abstract: OBJECTIVE
  TGF-β acts as a potent driver of cancer progression through the induction of epithelial-mesenchymal transition (EMT), in which epithelial cells acquire mesenchymal phenotype, leading to enhanced motility and invasion. Recent reports highlight the fundamental roles of TGF-β-induced EMT in multiple aspects of cancer progression. In this review, we focus on the novel insights into the roles of TGF-β-induced EMT in cancer progression and the underlying mechanisms that enable TGF-β to activate this epithelial plasticity response at transcription, translation, and posttranslational levels.
  
  
  RESULTS
  Smad-mediated transcription regulation is known to activate TGF-β-induced EMT. More recently, novel mechanisms of epigenetic control, alternative splicing, miRNAs, translation control, and posttranslational modifications have been shown to play key roles in the control of EMT. In addition to initiating carcinoma cell invasion, TGF-β-induced EMT can guide cancer cells to de-differentiate and gain cancer stem-cell-like properties. EMT also allows the generation of stromal cells that support and instruct cancer progression.
  
  
  CONCLUSIONS
  The differentiation plasticity of epithelial cells that mediates TGF-β-induced EMT and reversion from mesenchymal to epithelial phenotype are increasingly seen as integral aspects of cancer progression that contribute to survival and dissemination of cancer cells. Further mechanistic insights under physiological conditions may lead to new therapeutic or prognostic strategies in cancer treatment.
authors.affiliation: Department of Cell and Tissue Biology, Programs in Cell Biology and Developmental and Stem Cell Biology, University of California - San Francisco, San Francisco, California 94143-0669, USA.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Katsuno
authors.forename: Samy
authors.initials: S
authors.lastname: Lamouille
authors.forename: Rik
authors.initials: R
authors.lastname: Derynck
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000502:physiology; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology*
chemical_list: D016212:Transforming Growth Factor beta