Journal of Cell Science · 2005 · 386 citations · 54 references
Epithelium-to-mesenchyme TransitionCell GrowthCell JunctionsCellular PhysiologyIncreased MotilityEpithelial-mesenchymal TransitionMorphological ChangesTissue DevelopmentCell InteractionCadherin SwitchingCell SignalingMorphogenesisEpithelial-mesenchymal InteractionsAccompany EmtCell BiologyDevelopmental BiologySignal TransductionCell-matrix InteractionCell MigrationMedicineExtracellular Matrix
EMT involves morphological and behavioral changes, including downregulation of E‑cadherin and upregulation of N‑cadherin. This study aimed to determine how cadherin switching influences EMT in TGF‑beta1‑treated mammary epithelial cells. The authors induced EMT with TGF‑beta1 in mammary epithelial cells and examined cadherin expression. TGF‑beta1 induced EMT increased stress fibers and focal adhesions, decreased cell‑cell junctions, and these changes were reversible; cadherin switching was required only for increased motility, not for the morphological changes, as N‑cadherin knockdown did not alter morphology but reduced motility and morphological changes preceded E‑cadherin downregulation.
Epithelium-to-mesenchyme transitions (EMTs) are characterized by morphological and behavioral changes in cells. During an EMT, E-cadherin is downregulated while N-cadherin is upregulated. The goal of this study was to understand the role cadherin switching plays in EMT using a classical model system: transforming growth factor beta1 (TGF-beta1)-mediated EMT in mammary epithelial cells. We showed that stress fibers and focal adhesions are increased, and cell-cell junctions are decreased in response to TGF-beta1. Moreover, these changes were reversible upon removal of TGF-beta1. Downregulation of E-cadherin and upregulation of N-cadherin were both transcriptional. Neither experimental knockdown nor experimental overexpression of N-cadherin interfered with the morphological changes. In addition, the morphological changes associated with EMT preceded the downregulation of E-cadherin. Interestingly, TGF-beta1-induced motility in N-cadherin-knockdown cells was significantly reduced. Together, these data suggest that cadherin switching is necessary for increased motility but is not required for the morphological changes that accompany EMT.
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