Smad2 and Smad3, the intracellular mediators of transforming growth factor β （TGF-β） signaling, are directly phosphorylated by the activated type I receptor kinase, and then shuttle from the cytoplasm into the nucleus to regulate target gene expression. Here, we report that the 70-kDa heat-shock protein （HSP70） interacts with Smad2 and decreases TGF-β signal transduction. Ectopic expression of HSPT0 prevents receptor-dependent phosphorylation and nuclear translocation of Smad2, and blocks TGF-β-induced epithelial-mesenchymal transition （EMT） in HaCat cells. Our findings reveal an essential role of HSP70 in TGF-β-induced epithelial-mesenchymal transition （EMT） by impeding Smad2 phosphorylation.
