Transforming growth factor ß-induced epithelial to mesenchymal transition requires the Ste20-like kinase SLK independently of its catalytic activity.
Oncotarget
; 8(58): 98745-98756, 2017 Nov 17.
Article
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| MEDLINE
| ID: mdl-29228724
ABSTRACT
Invasion can be stimulated in vitro using the soluble ligand transforming growth factor-ß (TGFß) to induce a process called epithelial-to-mesenchymal transition (EMT) characterized by cell-cell junction breakdown and an invasive phenotype. We have previously demonstrated a role for Ste20-like kinase SLK cell migration and invasion. Here we show that SLK depletion in NMuMG mammary epithelial cells significantly impairs their TGFß-induced migration and invasion. Immunofluorescence studies show that a fraction of SLK localizes to E-cadherin-positive adherens junction and that SLK impairs the breakdown of cell-cell contacts. We find that SLK-depleted cultures express significantly lower levels of vimentin protein as well as Snai1 and E-cadherin mRNA levels following TGF-ß treatment. Surprisingly, our data show that SLK depletion does not affect the activation and nuclear translocation of Smad3. Furthermore, we show that expression of a dominant negative kinase does not impair tight junction breakdown and rescues Snai1 mRNA expression levels. Together these data suggest that SLK plays a novel role in TGFß-induced EMT, independent of Smads, in a kinase activity-independent manner.
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1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Oncotarget
Año:
2017
Tipo del documento:
Article
País de afiliación:
Canadá