Overexpression of heat shock protein 70 inhibits epithelial-mesenchymal transition and cell migration induced by transforming growth factor-β in A549 cells

Abstract

Heat shock protein 70 (HSP70) is a key member of the HSP family that contributes to a pre-cancerous environment; however, its role in lung cancer remains poorly understood. The present study used geranylgeranylacetone (GGA) to induce HSP70 expression, and transforming growth factor-β (TGF-β) was used to construct an epithelial-mesenchymal transition (EMT) model by stimulating A549 cells in vitro. Western Blot was performed to detect protein levels of NADPH oxidase 4 (NOX4) and the EMTassociated proteins E-cadherin and vimentin both before and after HSP70 expression. Cell morphological changes were observed, and the effect of HSP70 on cell migration ability was detected via the wound healing. The results demonstrated that GGA at 50 and 200 μmol/L could significantly induce HSP70 expression in A549 cells (P < 0.05). Furthermore, HSP70 induced by 200 μmol/L GGA significantly inhibited the changes of E-cadherin, vimentin, and cell morphology induced by TGF-β (P < 0.05), while HSP70 induced by 50 μmol/L GGA did not. The results of the wound healing assay indicated that 200 μmol/L GGA significantly inhibited A549 cell migration induced by TGF-β. Taken together, the results of the present study demonstrated that overexpression of HSP70 inhibited the TGF-β induced EMT process and changed the cell morphology and migratory ability induced by TGF-β in A549 cells.

Regulation of Epithelial and Endothelial Barriers by Molecular Chaperones

“…Similarly, depletion of another Hsp70 chaperone, HSPA8/Hsc70, in NRK-52E normal rat kidney epithelial cells decreased E-cadherin levels and diminished the assembly of E-cadherin-based AJs [41]. Consistent with the reported stabilizing effects of Hsp70 proteins on normal AJs, overexpression or pharmacological upregulation of these chaperones by geranylgeranylacetone (GGA) reversed the loss of E-cadherin expression and AJ disassembly in NRK-52E and A549 epithelial cells during the transforming growth factor (TGF)-β-induced epithelial to mesenchymal transition (EMT) [42,43]. HSPA1A/Hsp72 overexpression TGF-β-stimulated NRK-52E cells Attenuated TGF-β-induced decrease in E-cadherin expression [42] Induction of Hsp70s by geranylgeranylacetone (GGA) TGF-β-stimulated A549 cells Attenuated TGF-β-induced decrease in E-cadherin expression [43] HSPA1A/Hsp72 antisense knockdown Monochloramine-exposed Caco-2 colonic epithelial cells Promoted oxidant-induced decrease in TEER and an increase in the mannitol flux [44] HSPA1A/Hsp72 antisense knockdown…”

“…Similarly, depletion of another Hsp70 chaperone, HSPA8/Hsc70, in NRK-52E normal rat kidney epithelial cells decreased E-cadherin levels and diminished the assembly of E-cadherin-based AJs [ 41 ]. Consistent with the reported stabilizing effects of Hsp70 proteins on normal AJs, overexpression or pharmacological upregulation of these chaperones by geranylgeranylacetone (GGA) reversed the loss of E-cadherin expression and AJ disassembly in NRK-52E and A549 epithelial cells during the transforming growth factor (TGF)-β-induced epithelial to mesenchymal transition (EMT) [ 42 , 43 ].…”

Cell-Membrane-Coated and Cell-Penetrating Peptide-Conjugated Trimagnetic Nanoparticles for Targeted Magnetic Hyperthermia of Prostate Cancer Cells

“…85 Notably, tumor cells are more sensitive to temperature increment than normal cells, which makes hyperthermia an attractive tool for antitumor therapy. 86 In our study, PC-3 cells reacted to the CM-LN1-L-SSH MNPmediated hyperthermia by overexpressing the hsp70 protein: recently, a study showed that the overexpression of hsp70 proteins in A549 lung cancer cells leads to an inhibition of TGF-β signaling, which plays a significant role in cell migration reduction, 87 thus corroborating our findings. 3.8.…”