HSP70 decreases receptor-dependent phosphorylation of Smad2 and blocks TGF-β-induced epithelial-mesenchymal transition

Smad2 and Smad3, the intracellular mediators of transforming growth factor beta (TGF-beta) 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-beta signal transduction. Ectopic expression of HSP70 prevents receptor-dependent phosphorylation and nuclear translocation of Smad2, and blocks TGF-beta-induced epithelial-mesenchymal transition (EMT) in HaCat cells. Our findings reveal an essential role of HSP70 in TGF-beta-induced epithelial-mesenchymal transition (EMT) by impeding Smad2 phosphorylation.