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Updated: Jun 2, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
HSP70 decreases receptor-dependent phosphorylation of Smad2 and blocks TGF-β-induced epithelial-mesenchymal
Yihao Li1, Xianjiang Kang, Qiang Wang
1College of Life Sciences, Hebei University, Baoding 071002, China.
Abstract:
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 HSP70 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.
Insights
Heat shock protein 70 (HSP70) inhibits transforming growth factor beta (TGF-β) signaling by preventing Smad2 phosphorylation. This interaction blocks TGF-β-induced epithelial-mesenchymal transition (EMT), revealing HSP70
Area of Science:
- Cellular signaling pathways
- Molecular biology
- Protein interactions
Background:
- Transforming growth factor beta (TGF-β) signaling is crucial for cellular processes.
- Smad2 and Smad3 are key intracellular mediators of TGF-β signaling.
- TGF-β signaling regulates gene expression via Smad protein nuclear translocation.
Purpose of the Study:
- To investigate the role of 70-kDa heat-shock protein (HSP70) in TGF-β signal transduction.
- To determine if HSP70 affects Smad2 phosphorylation and nuclear translocation.
- To elucidate the impact of HSP70 on TGF-β-induced epithelial-mesenchymal transition (EMT).
Main Methods:
- Investigated the interaction between HSP70 and Smad2.
- Assessed the effect of HSP70 on TGF-β receptor-dependent Smad2 phosphorylation.
- Monitored Smad2 nuclear translocation in response to TGF-β.
- Examined the influence of HSP70 on TGF-β-induced EMT in HaCat cells.
Main Results:
- HSP70 directly interacts with Smad2.
- HSP70 expression decreases TGF-β signal transduction.
- Ectopic HSP70 expression prevents Smad2 phosphorylation and nuclear translocation.
- HSP70 blocks TGF-β-induced EMT in HaCat cells.
Conclusions:
- HSP70 plays a critical role in regulating TGF-β signaling.
- HSP70 acts as an inhibitor of TGF-β-induced EMT.
- HSP70 impedes TGF-β signaling by blocking Smad2 phosphorylation.
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