Transforming growth factor ?-induced epithelial to mesenchymal transition requires the Ste20-like kinase SLK independently of its catalytic activity.

ABSTRACT: Invasion can be stimulated in vitro using the soluble ligand transforming growth factor-? (TGF?) 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 TGF?-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-? 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 TGF?-induced EMT, independent of Smads, in a kinase activity-independent manner.

SUBMITTER: Conway J 

PROVIDER: S-EPMC5716764 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature