Heat shock protein 20 (HSPB6) regulates TNF-α-induced intracellular signaling pathway in human hepatocellular carcinoma cells

•HSP20 suppressed the growth of HCC cells in the presence of TNF-α.•HSP20 decreased the IKK-α expression in HCC cells.•HSP20 suppressed the TNF-α-stimulated NF-κB signaling in HCC cells.•The level of IKK-α was inversely proportional to that of HSP20 in human HCC tissue specimens.•HSP20 down-regulate...

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Veröffentlicht in:Archives of biochemistry and biophysics 2015-01, Vol.565, p.1-8
Hauptverfasser: Nagasawa, Tomoaki, Matsushima-Nishiwaki, Rie, Yasuda, Eisuke, Matsuura, Junya, Toyoda, Hidenori, Kaneoka, Yuji, Kumada, Takashi, Kozawa, Osamu
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Sprache:eng
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Zusammenfassung:•HSP20 suppressed the growth of HCC cells in the presence of TNF-α.•HSP20 decreased the IKK-α expression in HCC cells.•HSP20 suppressed the TNF-α-stimulated NF-κB signaling in HCC cells.•The level of IKK-α was inversely proportional to that of HSP20 in human HCC tissue specimens.•HSP20 down-regulates the TNF-α-stimulated NF-κB signaling in HCC. We previously demonstrated that the expression of HSP20, a small heat shock protein, is inversely correlated with the progression of HCC. Inflammation is associated with HCC, and numerous cytokines, including TNF-α, act as key mediators in the progression of HCC. In the present study, we investigated whether HSP20 is implicated in the TNF-α-stimulated intracellular signaling in HCC using human HCC-derived HuH7 cells in the presence of TNF-α. In HSP20-overexpressing HCC cells, the cell growth was retarded compared with that in the control cells under long-term exposure of TNF-α. Because NF-κB pathway is the main intracellular signaling system activated by TNF-α, we investigated the effects of HSP20-overexpression of this pathway. The protein levels of IKK-α, but not IKK-β, in the HSP20-overexpressing cells were decreased. Short-term exposure to TNF-α-induced phosphorylation and degradation of IκB, and the phosphorylation and transactivational activity of NF-κB were suppressed in the HSP20-overexpressing HCC cells. Furthermore, the increase in IKK-α levels was accompanied by a decrease in the HSP20 levels in human HCC tissues. These findings strongly suggest that HSP20 might decrease the IKK-α protein level and that it down-regulates the TNF-α-stimulated intracellular signaling in HCC, thus resulting in the suppression of HCC progression.
ISSN:0003-9861
1096-0384
DOI:10.1016/j.abb.2014.10.010