Hsc70 is required for E-cadherin expression in epithelial-like NRK-52E cells.
Heat-shock cognate protein 70 (Hsc70), a molecular chaperone, is involved in multiple cellular functions. We previously demonstrated that Hsc70 is required for TGF-β-induced Smad signaling in mesenchymal-like NRK-49F cells. In the present study, to compare the Hsc70 functions in TGF-β-related signaling between epithelial and mesenchymal cells, we examined the effect of Hsc70 downregulation on TGF-β-induced signaling in epithelial-like NRK-52E cells. TGF-β-induced Smad signaling was suppressed in cells treated with small interfering RNA (siRNA) for Hsc70. Interestingly, despite interference with TGF-β signaling, TGF-β-induced suppression of E-cadherin expression was not affected by Hsc70 knockdown. Instead, Hsc70 knockdown itself caused the suppression of E-cadherin expression at the transcription level in cells treated with Hsc70 siRNA. We also examined the effects of Hsc70 knockdown on the level of E-cadherin-gene repressors, such as Snail1, Slug, Zeb1, Zeb2, and Twist1, and found that transcription of the repressors was upregulated after 24- or 36-h treatment with Hsc70 siRNA. Collectively, these results indicate that, in addition to a supportive role in TGF-β-induced signaling, Hsc70 supports E-cadherin expression through downregulation of the E-cadherin-gene repressors in NRK-52E cells, suggesting that Hsc70 plays a functional role to maintain the epithelial cell phenotype.
['Ikezaki|Midori|M|', 'Nishioka|Naoki|N|', 'Nishikawa|Taro|T|', 'Higashimoto|Natsuki|N|', 'Ihara|Yoshito|Y|']
D000818:Animals D015820:Cadherins D002460:Cell Line D015536:Down-Regulation D004847:Epithelial Cells D015870:Gene Expression D050883:HSC70 Heat-Shock Proteins D034622:RNA Interference D051381:Rats D015398:Signal Transduction D051785:Smad Proteins D016212:Transforming Growth Factor beta D015854:Up-Regulation
Hsc70 E-cadherin Smad TGF-β Epithelial cells